Bioengineered Microbial Spores

ABSTRACT

Phenotypically modified bioengineered microbial spores are provided. The microbial spores may be used in various spore-based technologies such as probiotics, biomaterials and vaccines.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Application No.63/056,297 filed on Jul. 24, 2020, which is incorporated herein byreference in its entirety.

SEQUENCE LISTING

A sequence listing, filed as the ASCII text file“01001-008655-US1_SL.txt”, created on Jul. 9, 2021 and having a filesize of 276 kilobytes, is incorporated herein by reference in itsentirety.

FIELD OF THE INVENTION

The present invention relates to genetically intact bioengineeredmicrobial spores such as bacterial spores.

BACKGROUND

Bioengineering continues to offer solutions to problems in agriculture,industry, medicine, and environment. Numerous technologies have beendeveloped through genetic edition, such as metabolic engineering,¹bacterial spore-based vaccines,² cell-based therapies,^(3,4)herbicide-resistant crops,⁵ and biosensors,⁶ among others.⁷ Nonetheless,despite continuing advances, the full potential of genome editingremains unexploited. This is in part due to policies in place that varyin a case by case manner,⁸ and also due to consumers'preferences.^(9,10)

To promote broader adoption of bioengineered organisms derived fromgenome editing, several biosafety tools have been developed over thepast decade. One of these tools includes the use of RNA molecules togenerate temporary physiological changes in an organism of interest,thus completely avoiding genome edition.¹¹ However, these RNA-basedtechnologies have limitations including short endurance of the phenotypeinduced and the inability to express exogenous genes. Another approachis biocontainment, which consists of synthetic gene circuits that makethe survival of an organism dependent on laboratory conditions orspecific stimuli.¹²⁻¹⁴ However, organisms programmed for biocontainmentare based on genetic edition. Furthermore, the death of such an organismin the environment presents the risk of releasing its DNA, which canlater be absorbed by other microorganisms that are naturallycompetent,¹⁵ thus raising new concerns.

Genetic editing of B. subtilis (spores) has allowed scientists to createspore-based technologies such as probiotics, biomaterials, and vaccinesthat offer unique solutions due to the qualities that spores posses. Forexample, spores can be stored for long periods of time, they are easyand cheap to produce, and they are easily engineered, mainly through theexpression of proteins on their spore coats. However, concerns on thesafety of products that contain synthetic DNA may keep consumers awayfrom these technologies.

The present disclosure offers a solution to this problem by establishinga method to engineer spores where the final product is spores withengineered phenotypes, but wild type genetics. In the context ofbioengineering with synthetic gene circuits, our approach introduces abioengineering tool that leverages differential expression patterns indifferent compartments of an organism. The synthetic gene circuits areprogrammed to behave differently in different cellular compartments byresponding to natural differences in expression patterns,^(18,19)without relying on the addition of chemicals or promoter inducers.

SUMMARY

The present disclosure provides for a method of producing a modifiedmicrobial spore. The method may comprise: (a) introducing at least onevector into a spore-forming microorganism, wherein the at least onevector encodes (i) a sequence-specific endonuclease system which targetsthe at least one vector, and (ii) an exogenous gene product, wherein theendonuclease system is operably linked to a spore-specific promoter, and(b) culturing the spore-forming microorganism to generate a modifiedmicrobial spore.

The at least one vector may further encode an exonuclease.

The at least one vector may comprise a vector encoding thesequence-specific endonuclease system and the exogenous gene product.The at least one vector may comprise two vectors encoding thesequence-specific endonuclease system and the exogenous gene product ondifferent vectors.

The spore-forming microorganism may be a spore-forming bacterium or aspore-forming fungus. The spore-forming bacterium may be Bacillussubtilis, Bacillus firmus, Bacillus megaterium, Bacillusamyloliquefaciens, Bacillus licheniformis, or Bacillus pumilus.

The sequence-specific endonuclease system may comprise an RNA-guidedendonuclease. In one embodiment, the RNA-guided endonuclease comprises aCRISPR/Cas system. In one embodiment, the RNA-guided DNA endonuclease isa Cas enzyme or a variant thereof, such as Cas9. In one embodiment, theat least one vector encodes a Cas enzyme and a guide RNA (gRNA). In oneembodiment, the at least one vector encodes a Cas enzyme and two gRNAs.

In certain embodiments, the spore-specific promoter is PsspA.

In certain embodiments, the exonuclease is D15.

The at least one vector may be one or more plasmids.

The present disclosure provides for a phenotypically modified microbialspore. The spore may comprise an exogenous gene product (e.g.,associated with the spore coat), where the microbial spore is free ofexogenous genes, or substantially free of exogenous genes. The spore maynot be genetically engineered.

The microbial spore may be a bacterial spore or a fungal spore.

The exogenous gene product may be a protein. The exogenous gene productmay be an enzyme.

Also encompassed by the present disclosure is a composition comprisingthe microbial spore.

BRIEF DESCRIPTION OF THE DRAWINGS

The patent or application file contains at least one drawing executed incolor. Copies of this patent or application publication with colordrawing(s) will be provided by that Office upon request and payment ofthe necessary fee.

The following drawings form part of the present specification and areincluded to further demonstrate certain aspects of the presentdisclosure, which can be better understood by reference to one or moreof these drawings in combination with the detailed description ofspecific embodiments presented herein.

FIGS. 1A-1C. Schematization of the method to engineer spores whileleaving the genome intact. (FIG. 1A) Self-digestion circuit.Cas9g1/g2=Cas9+one or two sgRNAs, respectively; D15=D15 exonuclease;PsspA=sporulation specific promoter; TS=endonuclease target site;T=transcriptional terminator; ori=replication origin; FPs=genes encodingforeign proteins. (FIG. 1B) Events derived from the plasmid duringsporulation of B. subtilis. Circles=foreign proteins. (FIG. 1C) Finalproduct: engineered spores with intact genomes.

FIGS. 2A-2F. Stability of plasmids during growth and sporulation. (FIGS.2A, 2B) Bacterial growth in LB media. (FIGS. 2C, 2D) Adaptation to DSM.(FIGS. 2E, 2F) Sporulation in DSM. pBb is the backbone vector from whichthe rest of the plasmids built in this study are derived.Cas9g1/Cas9g2=Cas9+one or two sgRNAs, respectively. D15=D15 exonuclease.GFP=CotB-GFP fusion protein for expression of GFP in the spore coat.KinA=histidine kinase that induces sporulation artificially whenoverexpressed. Plasmid pLS1 was used as a control to assess whether ourexperiment was able to detect plasmid instability. *=controls whereplasmid self-digestion was not expected. **=control where plasmid losswas expected.

FIGS. 3A-3D. GFP-coated spores. FIGS. 3A, 3B: pCas9g1-D15-GFP spores.FIGS. 3C, 3D: Mix of pCas9g1-D15-GFP and WT spores. FIGS. 3A, 3C: GFPimaging with confocal microscopy. FIGS. 3B, 3D: Optical microscopy. Redarrows in FIGS. 3C and 3D indicate spores without GFP fluorescence,which correspond to the WT strain.

FIGS. 4A-4B. Atomic force microscopy of WT and pCas9g1-D15-KinA spores.FIG. 4A: WT spores. FIG. 4B: KinA spores. Spores shown have an averagediameter of ˜0.65 μm, and average length of 1.66 μm. Scale bar, 0.5 μm.

FIGS. 5A-5C. Germination of spores in LB or Valine media, and growth inLB-agar with or without antibiotic. Cm=chloramphenicol.

FIG. 6 . Map of plasmid pV1.

FIG. 7 . Map of plasmid pV1RX.

FIG. 8 . Map of plasmid pBb.

FIG. 9 . Map of plasmid pV1-PsspA.

FIG. 10 . Map of plasmid pCas9g1-cons.

FIG. 11 . Map of plasmid pCas9g2-cons.

FIG. 12 . Map of plasmid pCas9g1-D15-cons.

FIG. 13 . Map of plasmid pCas9g2-D15-cons.

FIG. 14 . Map of plasmid pCas9g1.

FIG. 15 . Map of plasmid pCas9g2.

FIG. 16 . Map of plasmid pCas9g1-D15.

FIG. 17 . Map of plasmid pCas9g2-D15.

FIG. 18 . Map of plasmid pCas9g1-D15-mut.

FIG. 19 . Map of plasmid pCas9g2-D15-mut.

FIG. 20 . Map of plasmid pCas9g1-D15-GFP.

FIG. 21 . Map of plasmid pCas9g2-D15-GFP.

FIG. 22 . Map of plasmid pCas9g1-D15-KinA.

FIG. 23 . Map of plasmid pCas9g2-D15-KinA.

FIGS. 24A-24D. GFP-coated spores. FIGS. 24A, 24C: GFP imaging withconfocal microscopy. FIGS. 24B, 24D: Optical microscopy. FIGS. 24A, 24B:Strain pCas9g1-D15-GFP. FIGS. 24C, 24D: Strain pCas9g2-D15-GFP.

FIGS. 25A-25C. Germination of spore strains corresponding to mutatedplasmids that were retained. Growth in LB-agar with or withoutantibiotic. Cm=chloramphenicol.

DETAILED DESCRIPTION

The present disclosure provides for methods to produce phenotypicallyengineered microbial spores with wild type genetics. For example, thespores may contain exogenous proteins on their spore coats. Theengineered microbial spores may be used in various spore-basedtechnologies in agriculture, medicine, and industry such as probiotics,biomaterials (e.g., energy converting materials, living materialsystems, etc.) and vaccines.

In certain embodiments, B. subtilis spores produced by the methodsexpress recombinant proteins while maintaining wild type genetics. Themethods may utilize plasmids which self-digest following sporulation,after expression of the desired protein(s) is complete. In certainembodiments, the methods can produce recombinant protein-expressingspores that contain no detectable plasmid or chromosome alteration.

The present disclosure provides for a method of producing a modifiedmicrobial spore. The method may comprise: (a) introducing at least onevector into a spore-forming microorganism, wherein the at least onevector encodes (i) a sequence-specific endonuclease system which targetsthe at least one vector, and (ii) an exogenous gene product, wherein theendonuclease system is operably linked to a spore-specific promoter, and(b) culturing the spore-forming microorganism to generate a modifiedmicrobial spore.

The at least one vector may further encode an exonuclease, such as D15.

The at least one vector may comprise a vector encoding thesequence-specific endonuclease system and the exogenous gene product.The at least one vector may comprise two vector encoding thesequence-specific endonuclease system and the exogenous gene product ontwo different vectors.

The spore-forming microorganism may be a spore-forming bacterium or aspore-forming fungus. For example, the spore-forming bacterium may beBacillus subtilis, Bacillus firmus, Bacillus megaterium, Bacillusamyloliquefaciens, Bacillus licheniformis, or Bacillus pumilus.

The sequence-specific endonuclease system may comprise an RNA-guidedendonuclease, such as a CRISPR/Cas system. The RNA-guided DNAendonuclease may be a Cas enzyme or a variant thereof, such as Cas9. Theat least one vector may encode a Cas enzyme and at least one guide RNA(gRNA) (e.g., a gRNA, two gRNAs, three gRNAs, etc.) which targets the atleast one vector.

The at least one vector may be a plasmid.

Also encompassed by the present disclosure is a phenotypically modifiedmicrobial spore, comprising an exogenous gene product, wherein themicrobial spore is substantially free of exogenous genes.

The microbial spore may be a bacterial spore or a fungal spore.

The exogenous gene product may be a protein, a polypeptide, or apeptide. The exogenous gene product may be an enzyme.

The present disclosure also provides for a composition comprising thepresent modified microbial spore.

The present compositions may be used in probiotics for humanconsumption, antibody production for therapeutic use, vaccines (e.g.,oral vaccines for livestock), production of recombinant proteins forbiological research, environmental remediation, fertilizer additives,etc.

The exogenous gene product (e.g., a protein) may be expressedcytoplasmically in a microbial cell, e.g., in soluble form, duringvegetative growth of the cell. The exogenous gene product, while made asa soluble material, becomes associated with spores during thesporulation process. In certain embodiments, the exogenous gene productmay be expressed as a fusion product with a spore coat protein whichwill be displayed on the spore surface. The term “associated” as usedherein may refer to the physical relationship of exogenous gene productto a spore, or a portion thereof. During sporulation, the exogenous geneproduct is produced during vegetative phase of cell growth and isphysically associated with the spore. The exogenous gene product may bedisplayed on the spore's surface, or may be entrained or entrappedwithin the spore coat.

Microorganisms or microbes include, but are not limited to, the twoprokaryotic domains, Bacteria and Archaea, as well as eukaryotic fungiand protists. By way of example, the microorganisms may includeProteobacteria (such as Pseudomonas, Enterobacter, Stenotrophomonas,Burkholderia, Rhizobium, Herbaspirillum, Pantoea, Serratia, Rahnella,Azospirillum, Azorhizobium, Azotobacter, Duganella, Delftia,Bradyrhizobiun, Sinorhizobium and Halomonas), Firmicutes (such asBacillus, Paenibacillus, Lactobacillus, Mycoplasma, and Acetobacterium),Actinobacteria (such as Streptomyces, Rhodococcus, Microbacterium, andCurtobacterium), and the fungi Ascomycota (such as Trichoderma,Ampelomyces, Coniothyrium, Paecoelomyces, Penicillium, Cladosporium,Hypocrea, Beauveria, Metarhizium, Verticullium, Cordyceps, Pichea, andCandida, Basidiomycota (such as Coprinus, Corticium, and Agaricus) andOomycota (such as Pythium, Mucor, and Mortierella).

Bacteria from the genus Bacillus include, but are not limited to,Bacillus subtilis, Bacillus firmus, Bacillus megaterium, Bacillusamyloliquefaciens, Bacillus brevis, Bacillus clausii, Bacillus lentus,Bacillus uniflagellatus, B. vallismortis, Bacillus lateropsorus,Bacillus laterosporus BOD, Bacillus megaterium, Bacillus polymyxa,Bacillus licheniformis, Bacillus pumilus, and Bacillussterothermophilus, Bacillus simplex, Bacillus sphaericus, Bacillusstearothermophilus, Bacillus thuringiensis, Bacillus coagulans, Bacillusthermophilus, Bacillus mycoides, Bacillus cereus, Bacillus circulans, orany combination thereof. In certain embodiments, the bacterial spore isBacillus thurengiensis var. aizawai, Bacillus licheniformis var.endoparasiticus, or Bacillus thuringiensis var. kurstaki.

The microbial spore may be a bacterial spore or a fungal spore.Bacterial spores may include endospores and akinetes. Fungal spores mayinclude statismospores, ballistospores, autospores, aplanospores,zoospores, mitospores, megaspores, microspores, meiospores,chlamydospores, urediniospores, teliospores, oospores, carpospores,tetraspores, sporangiospores, zygospores, basidiospores, asco spores,and asciospores.

As used herein, the term “phenotype” refers to the observablecharacteristics of a individual cell (e.g., a microorganism), cellculture, organism, or group of organisms. In some embodiments, thephenotypically modified spore has at least one heterologous trait. Asused herein, the term “heterologous trait” refers to a phenotypeimparted to a modified spore, not by an exogenous DNA, heterologouspolynucleotide or heterologous nucleic acid.

As used herein, the term “endogenous” or “endogenous gene,” refers tothe naturally occurring gene, in the location in which it is naturallyfound within the host cell.

As used herein, the term “exogenous” may refer to a substance comingfrom some source other than its native source. For example, the terms“exogenous protein,” or “exogenous gene” refer to a protein or gene froma non-native source or location, and that have been artificiallysupplied to a biological system.

As used herein, “promoter” refers to a DNA sequence capable ofcontrolling the expression of a coding sequence or functional RNA. Thepromoter sequence may contain proximal and more distal upstreamelements.

As used herein, the term “operably linked” refers to the association ofnucleic acid sequences on a single nucleic acid fragment so that thefunction of one is regulated by the other. For example, a promoter isoperably linked with a coding sequence when it is capable of regulatingthe expression of that coding sequence (i.e., that the coding sequenceis under the transcriptional control of the promoter).

As used herein, the phrases “vector”, “recombinant construct”,“expression construct”, “construct”, and “recombinant DNA construct” areused interchangeably. A vector comprises an artificial combination ofnucleic acid fragments, e.g., regulatory and coding sequences that arenot found together in nature. For example, a vector may compriseregulatory sequences and coding sequences that are derived fromdifferent sources, or regulatory sequences and coding sequences derivedfrom the same source, but arranged in a manner different than that foundin nature. Such construct may be used by itself or may be used inconjunction with another vector. The choice of vector may be dependentupon the method that will be used to transform host cells as is wellknown to those skilled in the art. For example, a plasmid vector can beused. Vectors can be plasmids, viruses, bacteriophages, pro-viruses,phagemids, transposons, artificial chromosomes, and the like, thatreplicate autonomously or can integrate into a chromosome of a hostcell. A vector can also be a naked RNA polynucleotide, a naked DNApolynucleotide, a polynucleotide composed of both DNA and RNA within thesame strand, a poly-lysine-conjugated DNA or RNA, a peptide-conjugatedDNA or RNA, a liposome-conjugated DNA, or the like, that is notautonomously replicating.

In certain embodiments, the vector is or is not integrated into themicrobial chromosome (e.g., the bacterial chromosome).

Nucleic acids (e.g., vectors) can be delivered to a bacterial cell bytransformation, e.g., heat shock, electroporation, etc. In oneembodiment, bacterial cells are incubated in a solution containingdivalent cations (e.g., calcium chloride) under cold conditions, beforebeing exposed to a heat pulse (heat shock). The sequence-specificnuclease can be introduced into the cell in the form of a protein or inthe form of a nucleic acid encoding the sequence-specific nuclease, suchas a vector, an mRNA or a cDNA. Nucleic acids can be delivered as partof a larger construct, such as a plasmid or viral vector, or directly,e.g., by electroporation, lipid vesicles, viral transporters,microinjection, and biolistics.

The term “substantially free” of an agent should be understood asmeaning free of the agent, or that any amount of the agent present inthe spore is so low so as not to have any effect on the spore (e.g., onthe phenotype of the spore, and/or on the properties of the spore).

The term “about” in reference to a numeric value refers to ±10% of thestated numeric value. In other words, the numeric value can be in arange of 90% of the stated value to 110% of the stated value.

Bacterial Spores

In certain embodiments, the microorganism is an endospore-formingbacterium, for example, from the Bacilli and Clostridia genera. BothBacilli and Clostridia undergo a lifecycle involving growth(multiplication) of cells, conversion of cells to endospores (whichoccurs when the cells are stressed by, for example, lack of nutrients),activation of the endospores (which occurs when the endospores arere-exposed to nutrients), followed by germination of the endospores andfinally outgrowth of new vegetative cells (which occurs under continuedexposure to nutrients).

Bacteria may include, but are not limited to, species includingspore-forming members of the phylum Firmicutes and spore-forming membersof the phylum Actinobacteria as listed in Bergey's Manual of SystematicBacteriology, Second Edition (2009), hereby incorporated by reference inits entirety. Non-limiting examples of the bacterial species includeBacillus subtilis, Bacillus agri, Bacillus aizawai, Bacillus albolactis,Bacillus alcalophilus, Bacillus altitudinis, Bacillus alvei, Bacillusamyloliquefaciens, Bacillus aneurinolyticus, Bacillus anthracis,Bacillus aquaemaris, Bacillus atrophaeus, Bacillus boronophilus,Bacillus brevis, Bacillus butanolivorans, Bacillus caldolyyicus,Bacillus centrosporus, Bacillus cereus, Bacillus circulans, Bacillusclausii, Bacillus coagulans, Bacillus endoparasiticus, Bacillusendorhythmos, Bacillus firmus, Bacillus flavothermus, Bacillus formis,Bacillus fusiformis, Bacillus globigii, Bacillus infernus, Bacilluskurstaki, Bacillus lacticola, Bacillus lactimorbus, Bacillus lactis,Bacillus laterosporus, Bacillus larvae, Bacillus laterosporus, Bacilluslentimorbus, Bacillus lentus, Bacillus licheniformis, Bacillus medusa,Bacillus metiens, Bacillus megaterium, Bacillus mesentericus, Bacillusmojavensis, Bacillus mucilaginosus, Bacillus mycoides, Bacillus natto,Bacillus nigrificans, Bacillus pantothenicus, Bacillus popilliae,Bacillus polymyxa, Bacillus pseudoanthracis, Bacillus pumilus, Bacillusschlegelii, Bacillus siamensis, Bacillus spp., Bacillus simplex,Bacillus sphaericus, Bacillus sporothermodurans, Bacillusstearothermophilus, Bacillus subtilis, Bacillus thermoglucosidasius,Bacillus thuringiensis, Bacillus unifagellatus, Bacillus vulgatis,Bacillus weihenstephanensis, Clostridium thermocellum, Clostridiumljungdahlii, Clostridium acetobutylicum, Clostridium beijerinckii,Clostridium butyricum, Clostridium ljungdahlii, Clostridium butyricum,Pasteuria penetrans, Pasteuria thornei, Pasteuria nishizawae and aspecies of the genus Streptomyces.

Bacillus subtilis is a Gram-positive, catalase-positive bacteriumcommonly found in soil. Members of the genus Bacillus have the abilityto form tough, protective endospores, a characteristic which allows thespores of the organism to tolerate extreme environmental conditions, tobe heat resistant, and to quantitatively survive lengthy exposure to awide range of temperatures including freezing and boiling, without lossof viability.

As used herein, “spore” or “spores” may refer to structures produced bybacteria and fungi that are adapted for survival and dispersal. Sporesare generally characterized as dormant structures; however, spores arecapable of differentiation through the process of germination.Germination is the differentiation of spores into vegetative cells thatare capable of metabolic activity, growth, and reproduction. Thegermination of a single spore results in a single fungal or bacterialvegetative cell. Fungal spores are units of asexual reproduction, and insome cases are necessary structures in fungal life cycles. Bacterialspores are structures for surviving conditions that may ordinarily benonconductive to the survival or growth of vegetative cells.

The term “Bacillus spore” in relation to Bacillus spore cell relatesherein to a spore that may be characterized as a dormant, tough,non-reproductive structure produced by Bacillus bacteria. The primaryfunction of spores is generally to ensure the survival of a bacteriumthrough periods of environmental stress. They are therefore resistant toultraviolet and gamma radiation, desiccation, lysozyme, temperature,starvation, and chemical disinfectants. Spores are commonly found insoil and water, where they may survive for long periods of time. Thespore coat is impermeable to many toxic molecules and may also containenzymes that are involved in germination. The core has normal cellstructures, such as DNA and ribosomes, but is metabolically inactive.When a bacterium detects that environmental conditions are becomingunfavorable it may start the process of sporulation, which takes abouteight hours.

Sporulation Promoter

A sporulation promoter may also be referred to as a sporulation-specificpromoter or spore-specific promoter.

The nuclease (e.g., the sequence-specific endonuclease) may be operablylinked to, or under the control of, a sporulation promoter which willcause expression of the nuclease in the spore (e.g., the forespore, orthe endospore). Sporulation promoters may be a fragment or variant of apromoter which remains transcriptionally active during sporulation.

In certain embodiments, the sporulation promoter is PsspA.

The sporulation promoter may be a native bclA promoter from a B. cereusfamily member. The sporulation promoter may comprise one or more sigma-Ksporulation-specific polymerase promoter sequences. Non-limitingexamples of sporulation promoters also include BclA promoter (B.anthracis Sterne), BetA promoter (B. anthracis Sterne), BAS1882 promoter(B. anthracis Sterne), Gene 3572 promoter (B. weihenstephensis KBAB 4),YVTN beta-propeller protein promoter (B. weihenstephensis KBAB 4), Cry1Apromoter (B. thuringiensis HD-73), ExsY promoter (B. thuringiensisserovar konkukian str. 97-27), CotY promoter (B. thuringiensis AlHakam), YjcA promoter (B. thuringiensis serovar kurstaki str. HD73),YjcB promoter (B. thuringiensis serovar kurstaki str. HD73), BxpBpromoter (B. thuringiensis Al Hakam), Rhamnose promoter (B.thuringiensis Al Hakam), CotY/CotZ promoter (B. anthracis Sterne), BclCpromoter (B. anthracis Sterne), Sigma K promoter (B. anthracis Sterne),InhA promoter (B. thuringiensis Al Hakam), BclA cluster glycosyltransferase operon 1 (B. thuringiensis serovar konkukian str. 97-27),BclA cluster glycosyl transferase operon 2 (B. thuringiensis serovarkurstaki str. HD73), and Glycosyl transferase promoter (B. thuringiensisAl Hakam). See, U.S. Pat. Nos. 11,044,916; 10,988,769; and 10,836,800,the content of each of which is incorporated herein by reference in itsentirety.

Nucleases

A nuclease can be an agent capable of cleaving a phosphodiester bondconnecting two nucleotide residues in a nucleic acid molecule. In someembodiments, a nuclease is a protein, e.g., an enzyme, that can bind anucleic acid molecule and cleave a phosphodiester bond connectingnucleotide residues within the nucleic acid molecule. A nuclease may bean endonuclease, cleaving phosphodiester bonds within a polynucleotidechain, or an exonuclease, cleaving phosphodiester bonds at the end ofthe polynucleotide chain. In some embodiments, a nuclease is asite-specific or sequence-specific nuclease (e.g., a sequence-specificendonuclease), binding and/or cleaving a specific phosphodiester bondwithin a specific nucleotide sequence, which is also referred to hereinas the “recognition sequence,” the “nuclease target site,” or the“target site.” In some embodiments, a nuclease is a RNA-guided nuclease,which is associated with (e.g., binds to) an RNA (e.g., a guide RNA,“gRNA”) having a sequence that can bind specifically to a target site,thereby providing the sequence specificity of the nuclease. Nucleasesmay be specific to either single-stranded or double-stranded nucleicacid sequences. Some enzymes have both exonuclease and endonucleaseproperties. In some embodiments, a nuclease recognizes a single strandedtarget site, while in other embodiments, a nuclease recognizes adouble-stranded target site, for example, a double-stranded DNA targetsite. The target sites of many naturally occurring nucleases, forexample, many naturally occurring DNA restriction nucleases, are wellknown to those of skill in the art. In many cases, a DNA nuclease, suchas EcoRI, HindIII, or BamHI, recognize a palindromic, double-strandedDNA target site of 4 to 10 base pairs in length, and cut each of the twoDNA strands at a specific position within the target site.

Endonucleases

Non-limiting examples of the site-specific endonucleases include a zincfinger nuclease (ZFN), a ZFN dimer, a ZFNickase, a transcriptionactivator-like effector nuclease (TALEN), meganucleases, or a RNA-guidedDNA endonuclease (e.g., CRISPR/Cas systems such as CRISPR/Cas9).Meganucleases are endonucleases characterized by their capacity torecognize and cut large DNA sequences (12 base pairs or greater). Anysuitable meganuclease may be used in the present methods, includingendonucleases in the LAGLIDADG and PI-Sce family.

In some embodiments, the sequence-specific endonuclease is a nickase.

The sequence-specific endonuclease of the methods and compositionsdescribed herein can be engineered, chimeric, or isolated from anorganism. Endonucleases can be engineered to recognize a specific DNAsequence, by, e.g., mutagenesis. Seligman et al. (2002) Mutationsaltering the cleavage specificity of a homing endonuclease, NucleicAcids Research 30: 3870-3879. Combinatorial assembly is a method whereprotein subunits form different enzymes can be associated or fused.Arnould et al. (2006) Engineering of large numbers of highly specifichoming endonucleases that induce recombination to novel DNA targets,Journal of Molecular Biology 355: 443-458. These two approaches,mutagenesis and combinatorial assembly, may be combined to produce anengineered endonuclease with desired DNA recognition sequence.

The term “RNA-guided nuclease” may refer to a nuclease that forms acomplex with (e.g., binds or associates with) one or more RNA that isnot a target for cleavage. The CRISPR (Clustered Regularly interspacedShort Palindromic Repeats) system exploits RNA-guided DNA-binding andsequence-specific cleavage of target DNA. The guide RNA/Cas combinationconfers site specificity to the nuclease. A single guide RNA (sgRNA) canbe complementary to a target sequence. The Cas (CRISPR-associated)protein binds to the sgRNA and the target DNA to which the sgRNA bindsand introduces a double-strand break. Typically, the bound RNA(s) isreferred to as a guide RNA (gRNA). gRNAs can exist as a complex of twoor more RNAs, or as a single RNA molecule. gRNAs that exist as a singleRNA molecule may be referred to as single-guide RNAs (sgRNAs), though“gRNA” is used interchangeably to refer to guide RNAs that exist aseither single molecules or as a complex of two or more molecules.Typically, gRNAs that exist as single RNA species comprise two domains:(1) a first domain that shares homology to a target nucleic acid (e.g.,a domain can direct binding of a Cas9 complex to the target); and (2) asecond domain that binds a Cas9 protein. In some embodiments, the seconddomain corresponds to a sequence known as a tracrRNA. In someembodiments, the RNA-programmable nuclease is the (CRISPR-associatedsystem) Cas9 endonuclease, for example Cas9 (Csn1) from Streptococcuspyogenes. The CRISPR/Cas9 system may comprise a Cas9 nuclease and anengineered crRNA/tracrRNA (or single guide RNA).

The terms “gRNA,” “guide RNA” and “CRISPR guide sequence” may be usedinterchangeably throughout and refer to a nucleic acid comprising asequence that determines the specificity of a Cas DNA binding protein ofa CRISPR/Cas system. A gRNA hybridizes to (complementary to, partiallyor completely) a target nucleic acid sequence. The gRNA or portionthereof that hybridizes to the target nucleic acid may be between 15-25nucleotides, 18-22 nucleotides, or 19-21 nucleotides in length. In someembodiments, the gRNA sequence that hybridizes to the target nucleicacid is 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 nucleotides inlength. In some embodiments, the gRNA sequence that hybridizes to thetarget nucleic acid is between 10-30, or between 15-25, nucleotides inlength.

In addition to a sequence that binds to a target nucleic acid, in someembodiments, the gRNA may also comprise a scaffold sequence. Expressionof a gRNA encoding both a sequence complementary to a target nucleicacid and scaffold sequence has the dual function of both binding(hybridizing) to the target nucleic acid and recruiting the endonucleaseto the target nucleic acid, which may result in site-specific CRISPRactivity. In some embodiments, such a chimeric gRNA may be referred toas a single guide RNA (sgRNA). As used herein, a “scaffold sequence,”also referred to as a tracrRNA, refers to a nucleic acid sequence thatrecruits a Cas endonuclease to a target nucleic acid bound (hybridized)to a complementary gRNA sequence.

In some embodiments, the gRNA sequence does not comprise a scaffoldsequence and a scaffold sequence is expressed as a separate transcript.In such embodiments, the gRNA sequence further comprises an additionalsequence that is complementary to a portion of the scaffold sequence andfunctions to bind (hybridize) the scaffold sequence and recruit theendonuclease to the target nucleic acid.

In one embodiment, Cas protein may be a functional derivative of anaturally occurring Cas protein.

Cas9 harbors two independent nuclease domains homologous to HNH and RuvCendonucleases, and by mutating either of the two domains, the Cas9protein can be converted to a nickase that introduces single-strandbreaks (Cong, L. et al. Science 339, 819-823 (2013)).

Cleavage of a target sequence may comprise cleaving one or two strandsat the location of the target sequence by the Cas enzyme. The methodsand compositions of the present disclosure may be used with the single-or double-strand-inducing version of Cas9, as well as with otherRNA-guided DNA nucleases, such as other bacterial Cas9-like systems. Thesequence-specific nuclease of the present methods and compositionsdescribed herein can be engineered, chimeric, or isolated from anorganism. The nuclease can be introduced into the cell in form of a DNA,mRNA and protein.

In some embodiments, the Cas endonuclease is a Cas9 enzyme or variantthereof. In some embodiments, the Cas9 endonuclease is derived fromStreptococcus pyogenes, Staphylococcus aureus, Neisseria meningitidis,Streptococcus thermophilus, or Treponema denticola. In some embodiments,the endonuclease is a Cas9 homolog or ortholog.

Alternatively or in addition, the Cas endonuclease is a Cpf1 nuclease.In some embodiments, the host cell expresses a Cpf1 nuclease derivedfrom Provetella spp. or Francisella spp.

In one embodiment, the CRISPR-Cas system for use in the methods providedherein is a Class 2 system. In one embodiment, the CRISPR-Cas system foruse in the methods provided herein is a Type II, Type V or Type VI Class2 system. In one embodiment, the CRISPR-Cas system for use in themethods provided herein is selected from Cas9, Cas12a, Cas12b, Cas12c,Cas12d, Cas12e, Cas13a, Cas13b, Cas13c or homologs, orthologs orparalogs thereof.

In some embodiments, the Cas proteins can comprise one or multiplenuclease domains. A Cas effector protein can target single stranded ordouble stranded nucleic acid molecules (e.g. DNA or RNA nucleic acids)and can generate double strand or single strand breaks. In someembodiments, the Cas effector proteins are wild-type or naturallyoccurring Cas proteins. In some embodiments, the Cas effector proteinsare mutant Cas proteins, wherein one or more mutations, insertions, ordeletions are made in a WT or naturally occurring Cas protein (e.g., aparental Cas protein) to produce a Cas protein with one or more alteredcharacteristics compared to the parental Cas protein.

In some instances, the Cas protein is a wild-type (WT) nuclease.Non-limiting examples of Cas proteins include C2c1, C2c2, C2c3, Cas1,Cas1B, Cas2, Cas3, Cas4, Cas5, Cash, Cas7, Cas8, Cas9 (also known asCsn1 and Csx12), Cas10, Cpf1, Csy1, Csy2, Csy3, Cse1, Cse2, Csc1, Csc2,Csa5, Csn2, Csm1, Csm2, Csm3, Csm4, Csm5, Csm6, Cmr1, Cmr3, Cmr4, Cmr5,Cmr6, Csb1, Csb2, Csb3, Csx17, Csx14, Csx100, Csx16, CsaX, Csx3, Csx1,Csx15, Csf1, Csf2, Csf3, Csf4, MAD1-20, SmCsm1, homologes thereof,orthologes thereof, variants thereof, mutants thereof, or modifiedversions thereof. Suitable nucleic acid guided Cas nucleases (e.g.,Cas9) can be from an organism from a genus including, but not limitedto: Thiomicrospira, Succinivibrio, Candidatus, Porphyromonas,Acidomonococcus, Prevotella, Smithella, Moraxella, Synergistes,Francisella, Leptospira, Catenibacterium, Kandleria, Clostridium, Dorea,Coprococcus, Enterococcus, Fructobacillus, Weissella, Pediococcus,Corynebacter, Sutterella, Legionella, Treponema, Roseburia, Filifactor,Eubacterium, Streptococcus, Lactobacillus, Mycoplasma, Bacteroides,Flaviivola, Flavobacterium, Sphaerochaeta, Azospirillum,Gluconacetobacter, Neisseria, Roseburia, Parvibaculum, Staphylococcus,Nitratifractor, Mycoplasma, Alicyclobacillus, Brevibacilus, Bacillus,Bacteroidetes, Brevibacilus, Carnobacterium, Clostridiaridium,Clostridium, Desulfonatronum, Desulfovibrio, Helcococcus, Leptotrichia,Listeria, Methanomethyophilus, Methylobacterium, Opitutaceae,Paludibacter, Rhodobacter, Sphaerochaeta, Tuberibacillus, andCampylobacter.

In some embodiments, the Cas endonuclease and the nucleic acid encodingthe gRNA are provided on the same nucleic acid (e.g., a vector). In someembodiments, the Cas endonuclease and the nucleic acid encoding the gRNAare provided on different nucleic acids (e.g., different vectors).Alternatively or in addition, the Cas endonuclease may be provided orintroduced into the cell in protein form.

In further embodiment, the endonuclease is a transcriptionactivator-like effector nuclease (TALEN). TALENs are composed of a TALeffector domain that binds to a specific nucleotide sequence and anendonuclease domain that catalyzes a double strand break at the targetsite (PCT Patent Publication No. WO2011072246; Miller et al., Nat.Biotechnol. 29, 143-148 (2011); Cermak et al., Nucleic Acid Res. 39, e82(2011)). Sequence-specific endonucleases may be modular in nature, andDNA binding specificity is obtained by arranging one or more modules.Bibikova et al., Mol. Cell. Biol. 21, 289-297 (2001). Boch et al.,Science 326, 1509-1512 (2009).

ZFNs can be composed of two or more (e.g., 2-8, 3-6, 6-8, or more)sequence-specific DNA binding domains (e.g., zinc finger domains) fusedto an effector endonuclease domain (e.g., the FokI endonuclease).Porteus et al., Nat. Biotechnol. 23, 967-973 (2005). Kim et al. (2007)Hybrid restriction enzymes: Zinc finger fusions to Fok I cleavagedomain, Proceedings of the National Academy of Sciences of USA, 93:1156-1160. U.S. Pat. No. 6,824,978. PCT Publication Nos. WO1995/09233and WO1994018313.

Exonucleases

In certain embodiments, the exonucleases used in the methods, systems,and compositions provided herein include exonucleases with a 5′ to 3′and/or a 3′ to 5′ exonuclease activity on a double-stranded DNA (dsDNA)substrate or single stranded DNA (ssDNA) substrate. In certainembodiments, the exonuclease will recognize a dsDNA substrate with ablunt end, including a blunt end with a 5′ phosphate group. In certainembodiments, the exonuclease will recognize a dsDNA substrate with anoverhang of ssDNA (e.g., a 5′ or 3′ ssDNA region at a terminus of adsDNA molecule, including ends produced by endonucleases which providestaggered cuts in dsDNA substrates). In certain embodiments, theexonuclease will recognize a dsDNA substrate having an internal break inone strand (e.g., a nicked dsDNA).

In one embodiment, the exonuclease is D15, an exonuclease from the T5phage.

Exonucleases with 5′ to 3′ exonuclease activity that can be used hereinalso include a bacteriophage lambda exo protein, an Rac prophage RecEexonuclease protein, an Artemis protein, an Apollo protein, a DNA2exonuclease protein, an Exo 1 exonuclease protein, a herpesvirus SOXprotein, UL12 exonuclease protein, an enterobacterial exonuclease VIIIprotein, a T7 phage exonuclease protein or a related protein withequivalent 5′ to 3′ exonuclease activity. Exonucleases with 3′ to 5′exonuclease activity that can be used herein include an E. coliExonuclease III, a mammalian Trex2 exonuclease protein, a relatedprotein with equivalent 3′ to 5′ exonuclease activity. In certainembodiments, the aforementioned exonucleases will comprise conservedDEDD catalytic residues characteristic of the DEDD/DnaQ superfamily ofexonucleases (Bernad et al., 1989). In certain embodiments, theexonuclease can comprise an allelic variant of any of the aforementionedexonucleases.

Applications of the Present Methods/Compositions

The present disclosure also provides for a composition comprising thepresent modified spore.

Compositions comprising microbial spores may be suitable foragricultural, horticultural, environmental, probiotic, aquatic,industrial and sanitation uses, among others. The present disclosureprovides microbial spore compositions (e.g., bacterial sporecompositions) for industrial uses such as agriculture, environmentalremediation, composting, methane production, cleaning supplies, oilrecovery, wastewater treatment, and direct fed microbials.

Regarding agricultural applications, the present composition may be usedto enhance the health of plants. The present compositions/spores may becoated onto seeds or other plant propagative material, such that oncesown or planted in an enhanced environment which supports germination ofthe seed, stimulation of plant growth or biological protection of theseed and resulting plant can be established. In one embodiment, thepresent composition may be used as, or in, a biopesticide.

The present composition may be for use in foods for human consumption orfor animal feed. In certain embodiments, the present disclosure providesfor a probiotic composition. In certain embodiments, the animal feed isa direct fed microbial. Probiotics are living microbes that havebeneficial effects on humans and/or animals when ingested. The probioticmay comprise the present composition and an acceptable carrier. Incertain embodiments, the bacterium is a spore-forming Bacillus specieswith probiotic effects. Representative examples of such spore-formingbacteria include various spore-forming Bacillus species including, butnot limited to, Bacillus species such as Bacillus subtilis, Bacilluslicheniformis, Bacillus coagulans, Bacillus pumilis, Bacillus clausii,mixtures thereof, and other microbes as described herein.

An acceptable carrier may be added to the composition. The acceptablecarrier may be a liquid carrier, a solid carrier, a water solublecarrier, or any other suitable carrier. In one embodiment, the liquidcarrier is milk or a milk replacer. Milk replacers are typically milksubstitutes in powdered form that are mixed with water to form acomposition that resembles milk. In one embodiment, the liquid carrieris water. Dry carriers include, but are not limited to, animal feed,whey, limestone (calcium carbonate), rice hulls, yeast culture, driedstarch, and sodium silico aluminate. In certain embodiments, the watersoluble carrier is selected from the group consisting of whey,maltodextrin, sucrose, dextrose, dried starch, and sodium silicoaluminate. In other embodiments, the acceptable carrier for a direct fedmicrobial is selected from the group consisting of vegetable oil,sucrose, silicon dioxide, polysorbate 80, propylene glycol, butylatedhydroxyanisole, citric acid, and ethoxyquin. In certain embodiments, theacceptable carrier is selected from the group consisting of animal feed,milk, yogurt, cheese, fermented milk, cereal, fermented cereal, juice,ice-cream, or a formulation for infants or children.

As used herein, “carrier”, “acceptable carrier”, or “pharmaceuticalcarrier” refers to a diluent, adjuvant, excipient, or vehicle. Suchcarriers can be sterile liquids, such as water and oils, including thoseof petroleum, animal, vegetable, or synthetic origin; such as peanutoil, soybean oil, mineral oil, sesame oil, and the like. Water oraqueous solution saline solutions and aqueous dextrose and glycerolsolutions are preferably employed as carriers, in some embodiments asinjectable solutions. Alternatively, the carrier can be a solid dosageform carrier, including but not limited to one or more of a binder (forcompressed pills), a glidant, an encapsulating agent, a flavorant, and acolorant. The choice of carrier can be selected with regard to theintended route of administration and standard pharmaceutical practice.In some aspects, carriers may be granular in structure, such as sand orsand particles. In further aspects, the carriers may be dry, as opposedto a moist or wet carrier. In some aspects, carriers can be nutritivesubstances and/or prebiotic substances selected fromfructooligosaccharides, inulins, isomalto-oligosaccharides, lactitol,lactosucruse, lactulose, pyrodextrines, soy oligosaccharides,transgalacto-oligosaccharides, xylo-oligosaccharides, and vitamins. Insome aspects, carriers can be in solid or liquid form. In some aspects,carriers can be zeolites, calcium carbonate, magnesium carbonate,trehalose, chitosan, shellac, albumin, starch, skim-milk powder,sweet-whey powder, maltodextrin, lactose, and inulin. In some aspects, acarrier is water or physiological saline.

In another aspect, the present disclosure relates to a method fortreating water in an aquaculture system, comprising contacting acomposition comprising a bacterial spore with water in an aquaculturesystem. In certain embodiments, the aquaculture system comprises ananimal.

The present composition may be used for animal feeds. The presentdisclosure relates to a method for feeding an animal comprisingadministering a composition comprising a bacterial spore to an animal.In certain embodiments, the animal is selected from the group consistingof poultry, ruminants, calves, pigs, rabbits, horses, crustaceans,mollusks, fish and pets. In another aspect, the present disclosurerelates to a method for feeding an animal in an aquaculture system,comprising administering an animal feed comprising a compositioncomprising a bacterial spore to the animal in the aquaculture system.The animal may be fish, shrimp, or mollusks. In certain embodiments, theaquaculture system comprises a pathogen selected from the groupconsisting of a Vibrio species, an Aeromonas species and aFlavobacterium species. In certain embodiments, the composition is inthe form of granules, briquettes, pellets, tablets, or capsules.

The present composition may be used for wastewater treatment, and thepresent disclosure relates to a method for treating wastewatercomprising adding a composition comprising a microbial spore (e.g., abacterial spore) to wastewater.

The present composition may be used for environmental remediation. Thepresent disclosure relates to a method for environmental remediationcomprising applying a composition comprising a microbial spore (e.g., abacterial spore) to soil or water. Bacillus species may be used forenvironmental remediation both in water and land. The bacteria breakdown chemicals and pollutants via enzyme and acid generation thatfurther break down the pollutant or bind it in a more non-reactive form.

The present disclosure relates to a cleaning product comprising acomposition comprising the present spore (e.g., the bacterial spore) andan acceptable carrier. In certain embodiments, the acceptable carrier isselected from the group consisting of a detergent, a soap, and afragrance. In certain embodiments, the cleaning compounds is for use inbathrooms and transit areas.

The present disclosure provides for a method of producing methane fromwaste material, comprising applying a composition comprising the presentspore (e.g., the bacterial spore) to waste material.

The present disclosure relates to a method of treating animal waste,bedding or litter comprising applying a composition comprising thepresent spore (e.g., the bacterial spore) to animal waste, bedding orlitter.

In another aspect, the present disclosure relates to a method ofpreparing silage comprising applying a composition comprising thepresent spore (e.g., the bacterial spore) to silage.

The present disclosure relates to a method for microbial enhanced oilrecovery (MEOR), comprising applying a composition comprising thepresent spore (e.g., the bacterial spore) to an oil well. In certainembodiments, the bacterial spore is Bacillus subtilis, Bacilluslicheniformis, Bacillus mojavensis, and other microbes described herein.U.S. Pat. No. 9,610,333.

The present composition may be a pharmaceutical composition. The presentdisclosure relates to a method of treating or preventing adisease/condition in a subject susceptible to or afflicted with thedisease/condition. The method may comprise administering to the subjectan effective amount of the present composition (comprising a microbialspore such as a bacterial spore or a fungal spore). In certainembodiments, the disease is a bacterial disease, a fungal disease or aviral disease. In certain embodiments, the disease is necroticenteritis. In certain embodiments, the subject is a human. In certainembodiments, the subject is a non-human animal. In certain embodiments,the subject is a chicken, a turkey or a duck. In certain embodiments,the subject is selected from the group consisting of fish, shrimp, ormollusks. In certain embodiments, the subject is infected withClostridium perfringens. In certain embodiments, treating or preventingthe disease results in one or more of reducing mortality, reducinglesion number, and increasing weight gain compared to a subject that isnot administered the composition.

The present modified spore may be used as a vehicle for heterologousantigen delivery and vaccination. In one embodiment, heterologousantigens displayed on the spore surface as a fusion product with sporecoat proteins can be used to elicit protective immune responses. Thecomposition may comprise the microbial spore and an adjuvant. Anadjuvant may be administered together with an antigen whichnonspecifically enhances the immune response to that antigen. Adjuvantsmay be insoluble and undegradable substances (e.g., inorganic gels suchas aluminum hydroxide), or water-in-oil emulsions such as incompleteFreund's adjuvant. Generally, adjuvants may retard the destruction ofantigen and allow the persistence of low but effective levels of antigenin the tissues and also nonspecifically activate the lymphoid system byprovoking an inflammatory response. One adjuvant is Freund's completeadjuvant having mycobacteria suspended in a water-in-oil emulsion. Forexample, the adjuvant may be cholera toxin, a non-toxic variant ofEscherichia coli labile toxin, and a portion or a derivative thereof.

The present modified spore may be used as a vehicle for drug and/orenzyme delivery where the drug and/or enzyme is the exogenous geneproduct (which may be associated with the spore coat).

The composition may be formulated to be administered by one or more ofthe following routes: intravenous, intramuscular, intraperitoneal,intradermal, intrapulmonary, intravaginal, rectal, oral, buccal,sublingual, intranasal, intraocular, and subcutaneous.

In certain embodiments, the composition is in the form of a dry powder.In certain embodiments, the composition is in the form of an emulsion.In certain embodiments, the compositions may be prepared in the forms ofgranules, briquettes, pellets, tablets, or capsules.

The present disclosure provides a kit comprising: a vector describedherein; or a composition described herein. The kit may compriseinstructions for using the vector, or the composition, in a methoddescribed herein. In a related embodiment, the kit further includes anapplicator for the composition, for example, a spray bottle, a nasalsprayer, a fluid dropper, an oral inhaler, a nasal inhaler, or asyringe.

An embodiment provides a vaccination kit that includes a unit dose ofthe composition according to any of embodiments herein, a container, andinstructions for use.

The following examples of specific aspects for carrying out the presentinvention are offered for illustrative purposes only, and are notintended to limit the scope of the present invention in any way.

Example 1

Developments in genome editing offer potential solutions to challengesin agriculture, industry, medicine, and the environment. However, manytechnologies remain unexploited due to limitations in the use ofgenetically altered organisms. In this study, we use B. subtilis sporesto explore the possibility of bioengineering organisms while leavingtheir genome intact. Taking advantage of the differential expressionbetween the mother cell and the fore-spore compartments duringsporulation, we created plasmids programmed to modify the sporephenotype from the mother cell compartment, but to “self-digest” in theforespore. At the end of sporulation, the mother cell undergoes lysisand releases the phenotypically engineered, genetically unalteredspores. Using this approach, we demonstrated the potential to expressforeign proteins in B. subtilis spores without genome alterations byproducing spores expressing GFP in their protective coats, whereapproximately 90% of the spore population had no detectable plasmid orchromosome alterations. In a separate demonstration, we programmed KinAoverexpression during vegetative growth to artificially inducesporulation, and also obtained spores with nearly 90% of them free ofdetectable plasmid. Artificial induction of sporulation couldpotentially simplify the bioprocess for industrial spore production, asit reduces the number of steps involved. Overall, these findingsdemonstrate the potential to create genetically intact bioengineeredorganisms.

In this work, we investigated the possibility of creating geneticallyintact bioengineered organisms by introducing synthetic gene circuits inplasmids that are deleted once the phenotype is completed. Plasmid DNAdigestion in vivo has been previously performed efficiently in thebacteria E. coli, although with different purposes that resulted in thefinal product carrying genome alterations.^(16,17) However, such studiesrevealed that plasmid DNA digestion in vivo is possible. In contrast tothese studies in which plasmid DNA digestion circuitry is introducedseparately by a phage¹⁶ or by integration into the chromosome,¹⁷ here wedeveloped a DNA digestion circuit that is self-contained in the targetplasmid that also carries the phenotype genes.

When the self-digestion circuit and phenotype genes are self-containedin the same plasmid, it becomes important to avoid DNA self-digestionbefore expression of the phenotype. The process of sporulation inBacillus offers an opportunity to exert control over self-digestion andphenotype expression due to differential expression in the mother celland the fore spore compartments during sporulation.^(18,19) Using B.subtilis spores as a model organism, we exploited differentialexpression by building plasmids that behave differently in eachcompartment by leveraging spore-specific promoters. The plasmids modifythe spore from the mother cell, while they suffer programmedself-digestion inside the fore-spore. This programmed self-digestion istriggered when the spore-specific promoters on the plasmid becomeactivated during sporulation. The promoters drive the expression of DNAnuclease genes which are also on the plasmid. Then, the DNA nucleasestarget the plasmid itself, cut it, and digest it. At the end ofsporulation, the mother cell undergoes lysis and releases thegenetically intact bioengineered spores.

In the context of bioengineering with synthetic gene circuits, ourapproach introduces a bioengineering tool that leverages differentialexpression patterns in different compartments of an organism. Thesynthetic gene circuits we developed in this work are programmed tobehave differently in different cellular compartments by responding tonatural differences in expression patterns,^(18,19) without relying onthe addition of chemicals or promoter inducers. The present method canalso be used in other organisms by harnessing differential expression ofgenes in different compartments and tissues. Here, this capability isexploited to modify the spore from the mother cell and self-digest theplasmid in the forespore upon activation of certain spore-specificpromoters.

Our approach is summarized in FIGS. 1A-1C. The plasmids we designedcontain a synthetic self-digestion gene circuit (FIG. 1A) that consistsof PsspA (a sporulation-specific promoter²⁰), Cas9g1 or Cas9g2 (acombination of the Cas9 gene and one or two different sgRNAs,respectively), and D15 (the exonuclease from the T5 phage²¹).Transcriptional terminators isolate the self-digestion circuit from therest of the genetic elements in the plasmid such as the origin ofreplication or other expression cassettes. Target sites, sequences meantto be targeted by Cas9g1 or Cas9g2, are located in the plasmid itself,close to the replication origin. Some plasmids additionally containexpression cassettes encoding foreign proteins, devised to modify thespore phenotype, and these are positioned outside the self-digestioncircuit. The promoter PsspA starts being active at time point T3 ofsporulation, and only inside the forespore.²⁰ By the stage T3, mothercell and fore-spore are already well-defined compartments, whichprevents Cas9 and D15 from digesting the plasmid in the mother cell. Inthe forespore, Cas9g1 or Cas9g2 recognize the target sites and linearizethe plasmid, which is later digested into single nucleotides by D15.Because the plasmid in the mother cell is intact, the foreign proteinsare expressed constitutively to modify the spore (FIG. 1B). By the endof sporulation, the mother cell is lysed, and the engineered spores arereleased and purified. The final product is engineered spores withintact genomes (FIG. 1C).

Using the self-digestion circuit, we created plasmids to either producespores expressing GFP in their protective coats, or overexpress KinA, ahistidine kinase that was previously reported to induce sporulationartificially. We first determined plasmid stability during vegetativegrowth and sporulation, and then we analyzed plasmid self-digestion oncesporulation was completed by quantifying average plasmid copy numbersper cell or per spore, respectively. Then we analyzed the presence ofplasmids in colonies generated from individual spores upon germinationby colony PCR. The results of these analyses showed that for both GFPexpressing and KinA overexpressing spores, approximately 90% of thespores contained no detectible plasmid. We further investigated thosecases in which plasmids were retained, and found that the plasmidscontained mutations in key elements of the self-digestion program.

Results and Discussion

Evaluation of Plasmid Self-Digestion at the Population Level ThroughqPCR.

To evaluate the success of the programmed self-digestion of theplasmids, we first quantified plasmid DNA in spores at the populationlevel. Reports of quantification of plasmid DNA in spores is limited toa small number of published studies.²²⁻²⁴ These studies show that whilesome plasmids are present in all spores,^(23,24) others such as pLS1,²⁴are unstable such that only a small fraction of the spore populationretained it. Plasmid stability in the mother cell is particularlyimportant because in all the reported engineered spore phenotypes, it isthe spore outer layers that get modified by proteins expressed in themother cell. Therefore, we first analyzed whether our plasmids werestable during vegetative growth and in the mother cell duringsporulation. After transforming B. subtilis with our plasmids, bacteriawas grown in LB media for 2 h, followed by growth in sporulation media(DSM) for 3 h, followed by sporulation in DSM for 24 h (withoutantibiotic in the three cases). Plasmid copy number (PCN) was quantifiedthrough each stage as described in the methods section, and we observedthat the plasmids were stable in the mother cell through all threestages, with the exception of plasmid pLS1 (FIGS. 2A-2F). The loss ofpLS1 was anticipated in agreement with previous reports that show thisplasmid to be unstable during vegetative growth in the absence ofantibiotic as selective pressure, while most of it is lost duringsporulation independently of the presence or absence of antibiotic,²⁴although the molecular mechanism by which this occurs remains obscure.In this experiment, we used pLS1 as a control that allowed us to test ifour experiment could detect plasmid instability.

After plasmid stability experiments, we transformed B. subtilis with thevarious plasmids and generated the different spore strains. Thesestrains were analyzed through qPCR, and the average PCN per spore wasdetermined and compared among strains to determine if plasmidself-digestion occurred. Three positive controls were used in this case:pBb (the Backbone plasmid used to build all the plasmids generated inthis study), and pCas9g1-D15-mut and pCas9g2-D15-mut (plasmids for whichthe promoter driving expression of the DNA nucleases was deleted). Ourresults showed that a significantly reduced PCN per spore was detectedin strains pCas9g1-D15, pCas9g2-D15, and variants from both (Table 1),while positive controls kept a higher PCN per spore. Strains that onlycontained the endonuclease showed no reduction in PCN per spore,suggesting that plasmid self-digestion occurred as a result of thecoupled activity of endonuclease and exonuclease.

TABLE 1 Average Plasmid Copy Number per Spore Plasmid to Components forchromo- self-digestion or some Plasmid generation of a phenotype ratiopBb^(a) 6.51 pLS1^(b) 0.02 pCas9g1 Cas9, and one sgRNA 5.33 pCas9g1-Cas9, one sgRNA, and D15 0.11 D15 pCas9g1- Cas9 and D15 with no 6.38D15-mut^(a) promoter, and one sgRNA pCas9g1- Cas9, one sgRNA, 0.21D15-GFP D15, and GFP pCas9g1- Cas9, one sgRNA, KinA 0.36 D15-KinApCas9g2 Cas9, and two sgRNAs 4.13 pCas9g2- Cas9, two sgRNAs, and 0.16D15 D15 pCas9g2- Cas9 and D15 with no 6.21 D15-mut^(a) promoter, and twosgRNAs pCas9g2- Cas9, two sgRNAs, 0.15 D15-GFP D15, and GFP pCas9g2-Cas9, two sgRNA, KinA 0.17 D15-KinA ^(a)Controls where plasmidself-digestion was not expected. ^(b)Control where plasmid loss wasexpected.

Evaluation of Plasmid Elimination at the Individual Cell Level ThroughColony PCR.

Although the experiments with qPCR report a substantial reduction inaverage PCN values, it does not allow the determination of the presenceand absence of plasmids in individual spores. To determine and count thenumber of individual plasmid-free spores, we germinated spores, allowingthem to replicate any plasmids retained, and then analyzed colonies forplasmid presence/absence through colony PCR. To achieve this, weheat-activated spores, germinated them in LB or valine media aspreviously described,²⁵ and plated them on LB-agar for development ofindividual colonies. The valine media was used because it allowsgermination of superdormant spores, which germinate poorly otherwise,even in the presence of other nutrients.²⁵ Germinating superdormantspores was important given that it is unknown if the presence of plasmidDNA in Bacillus affects the rate at which superdormant spores aregenerated. Thus, germinating superdormant spores assures a more preciseway of counting plasmid-free spores.

Colony PCR was performed with primers targeting a conserved region amongall our designer plasmids, and we found that nearly 90% of bacterialcolonies derived from strains pCas9g1-D15, pCas9g2-D15, and variantsfrom both, had no detectable plasmid (Table 2). On the other hand,plasmid was detected in all of the colonies derived from positivecontrol strains (pBb, pCas9g1-D15-mut, and pCas9g2-D15-mut). Similarly,plasmid was detected in all the colonies examined that derived fromplasmids that contained the Cas9 endonuclease, but not the D15exonuclease (pCas9g1 and pCas9g2).

TABLE 2 Ratio of Spores That Tested Negative for Plasmid Negativecolonies Plasmid LB Valine pBb^(a)  0/100  0/100 pLS1^(b) 96/100 99/100pCas9g1  0/100  0/100 pCas9g1-D15 89/100 88/100 pCas9g1-D15-mut^(a) 0/100  0/100 pCas9g1-D15-GFP 89/100 89/100 pCas9g1-D15-KinA 88/10084/100 pCas9g2  0/100  0/100 pCas9g2-D15 92/100 86/100pCas9g2-D15-mut^(a)  0/100  0/100 pCas9g2-D15-GFP 88/100 91/100pCas9g2-D15-KinA 87/100 86/100 ^(a)Controls where plasmid self-digestionwas not expected. ^(b)Control where plasmid loss was expected.

In contrast with our results, previous studies have achieved targetedplasmid digestion in vivo in E. coli with the use of the endonucleaseCas9 alone, without an additional exonuclease, ^(16,17) indicating thatthe elements necessary for successful DNA digestion in vivo may varyfrom host to host.

Another notable difference between our study and those performed in E.coli is the origin of the DNA digestion. While in our study the plasmidsare programmed to undergo self-digestion (cis-acting), the studiesmentioned above contain the DNA digestion program in a DNA moleculedistinct from the one being targeted (trans-acting). Therefore, theirsynthetic gene circuits continue to express the Cas9 indefinitely, whilein our study, the expression of Cas9 decreases as the amount or theintegrity of the target plasmids decrease. This could be part of thereason why the plasmid is retained in some spores, although we laterdemonstrate that various mutations arise during sporulation, and suchmay be the cause for plasmid retention. Note that in the studies in E.coli previously mentioned, the resulting bacteria cannot be classifiedas to have a wild type genome anymore.

In agreement with our strategy for having plasmids undergoself-digestion during sporulation, data from positive controls in qPCRand colony PCR experiments suggest that plasmid loss did not occurthroughout the processes of germination or growth for colony formation.Indeed, studies show that plasmid replication during germination tendsto be more robust than chromosome replication.^(24,26)

To further support the idea that plasmid loss occurred duringsporulation, we performed another experiment in which we comparedgermination and colony formation in media with or without antibiotic,for which the plasmids provide resistance (FIGS. 5A-5C). Thus, we wouldhave expected that if plasmid loss occurred during germination, positivecontrols would have shown fewer colonies in media with antibiotic thanin media without it. However, only strains pCas9g1-D15, pCas9g2-D15, andGFP and KinA derivatives showed fewer colonies, in agreement with qPCRresults, suggesting that plasmid loss occurred during sporulation.

Our analysis thus far focused on quantification of plasmids, but itcould also be possible that cells contain fragments of plasmid DNAintegrated into the chromosome. Although processes such asplasmid-chromosome recombination are known to be rare,²⁷ we neverthelessdeveloped a strategy to test plasmid integration into the chromosome(described in the Methods section). Because the prevalence of suchchromosome alterations are small, it is difficult to quantify theprecise fraction of cells that contain such alterations. Our tests donewith six different plasmids containing the self-digestion circuit showedthat out of the six hundred colonies tested, only five colonies haddetectible plasmid integration in the chromosome. (Tables 6-7).

TABLE 6 Plasmid integration into the chromosome Plasmid Colonies withrecombination pCas9g1-D15 0/100 pCas9g1-D15-GFP 1/100 pCas9g1-D15-KinA1/100 pCas9g2-D15 1/100 pCas9g2-D15-GFP 0/100 pCas9g2-D15-KinA 2/100

TABLE 7 Primers used for identification of plasmidintegration events through reverse PCR Oligo TargetOligo sequence (5′→3′) Plasmid(s) R001  1 CCTGAATAGAGTTCATAAACAATCC AllR002 TTCAGGAATTGTCAGATAGGCC R003  1A AACAATCCTGCATGATAACCATC R004GTCAGATAGGCCTAATGACTG R005  2 TGCAGGGTAAAATTTATATCCTTCT All R006TTAGTGACAAGGGTGATAAACTC R007  2A ATATCCTTCTTGTTTTATGTTTCGG R008AGGGTGATAAACTCAAATACAGC R009  3 TACGGTGTAAACCTTCCTCCA All R010TACACCGTAAAAGGTTAATCTCC R011  3A CCTCCAAATCAGACAAACGTTTC R012GGTTAATCTCCTATGGTGGTTTG R013  4 CATTGCTCTCCTCCAGTTGC All R014AATGAAACATGGCATTCAGTCAC R015  4A CAGTTGCACATTGGACAAAGC R016GTCACAAAAGGTTGTTGCTGAAG R017  5 CCTCTCGGTTATGAGTTAGTTC All R018AAGAACGAAGTCGAGATCAGG R019  5A GTTATGAGTTAGTTCAAATTCGTTC R020GTCGAGATCAGGGAATGAGTT R021  6 AACTCGGTCGCCGCATACA All R022TTGCCCGGCGTCAACACG R023  6A CCGCATACACTATTCTCAGAATG R024ACACGGGATAATACCGCGC R025  7 TAGTTATCTACACGACGGGGA All R026ACGATACGGGAGGGCTTAC R027  7A AGTCAGGCAACTATGGATGAAC R028CCATCTGGCCCCAGTGCT R029  8 GGATAAGGCGCAGCGGTC All R030GGTAACTATCGTCTTGAGTCC R031  8A AGCGGTCGGACTGAACGG R032GTCCAACCCGGAAAGACATG R033  9 AGCTATGAGATGGAGAAAGCC All R034TACCCAGGCTTAACCTTCTTC R035  9A GCCATAACCATGAGTGATAACAC R036CTTCTTCGGCTTTTTCACGAG R037 10 GCGTGTTCAGACTAGAACATC All R038CCCTTATCACCTAGAACAATCGT R039 10A ACCAGAGTATAAAGGTAATCGTG R040ATCGTAGTTCTGGCAGAGTAG R041 11 TGCTATTGCTGCTGTAGGTCA All R042CCACACAGTAGGTAGGTAAATC R043 11A CAAGATGTGTTAGATAAGTTCACG R044ATCAACCAGAATCAAGTTTCGGA R045 12 GATTGAGGGAGATTTAAATCCTG All R046CCAAATAGATTAAGCGCAAATCC R047 12A TCCTGATAATAGTGATGTGGACA R048CCGCTTTATCAGTAGAATCTACC R049 13 TTATATTGATGGGGGAGCTAGC All R050CATCAATATAACCTGCATATCCG R051 13A GGGGAGCTAGCCAAGAAGA R052CCTGCATATCCGTTTTTTGATTG R053 14 CCAGCATTTCTTTCAGGTGAAC All R054GGTTTTCGCATTCCTTCAGTAAC R055 14A GAACAGAAGAAAGCCATTGTTGA R056AACATATTTGACCTTTGTCAATTCG R057 15 GTCAAAGTAATGGGGCGGCA All R058TGTTCATGTAAACTATCGCCTTG R059 15A CGGCATAAGCCAGAAAATATCG R060CCTTGTCCAGACACTTGTGC R061 16 GGTTGAAACTCGCCAAATCAC All R062AATTGGCGTTTGATAAAACCAGC R063 16A AAATCACTAAGCATGTGGCACAA R064GCTTTATCAAGTTCACTCAAACC R065 17 CACAGTGCGCAAAGTATTGTC All R066CTGTGGCAAAATCTCGCCC R067 17A TCCATGCCCCAAGTCAATATTG R068CTCGCCCTTTATCCCAGACA R069 18 GCTAGTCATTATGAAAAGTTGAAGG All R070CACATATTTGCTTGGCAGAGC R071 18A GTTGAAGGGTAGTCCAGAAGA R072GCAGAGCCAGCTCATTTCC R073 19 GAGATCTGCAGTGACTGGGA pCas9g1-D15 R074ATCTCTAGAAGCTCCAGTCAC R075 19A CCTGGCGACTAGTCTTGGA R076TCACTGCAGATCTCTAGAAGC R077 20 GAGATCAGGTCAGACGCGAT pCas9g2-D15 R078ATCTCTAGAAGCTCCAGTCAC R079 20A GATTTCCTGGGTGCTCGAG R080TCACTGCAGATCTCTAGAAGC R081 21 CTCCATCTGGATTTGTTCAGAACpCas9g2-D, pCas9g2- R082 AGTTCTGAGGTCATTACTGGATC D15- R083 21AAGAACGCTCGGTTGCCGC GFP, pCas9g2-D15- R084 TGGATCTATCAACAGGAGTCC KinAR085 22 GCAAGCTTGACAAGTATTTCTTC pCas9g1-D15-GFP, R086TGCCATCTTAACCGGATAAGG pCas9g2- R087 22A GGAGGGCAAACTACTAGAGATG D15-GFPR088 GATAAGGAGATCATTGAGGAAGC R089 23 CGTGCTTGAGGCGGACGA pCas9g1-D15-GFP,R090 CACCGGTGTTTGTTCCTCGA pCas9g2- R091 23A ACGACCTGTCAGAAGTGTTCAD15-GFP R092 CGATCTTAAGGTCCGGTTCG R093 24 GCAGTAGCGACTACCAGAGpCas9g1-D15-GFP, R094 TGAGCTTTTGCTGCTCTGGTA pCas9g2- R095 24AACCAGAGTAGTCGTAGCCC D15-GFP R096 GGTAGTCGCTACTCTTCAGG R097 25GGAGGACGGAAACATTCTGG pCas9g1-D15-GFP, R098 TCGATTCCTTTGAGTTCAATACGpCas9g2- R099 25A TTCTGGGCCACAAACTGGAAT D15-GFP R100TACGGTTTACCAGGGTGTCG R101 26 TTGGTGAGAATCCAGGGGTC pCas9g1-D15-GFP R102GTTCTGAACAAATCCAGATGGAG R103 26A GGGGTCCCCAATAATTACGAT R104GGAGTTCTGAGGTCATTACTG R105 27 CGCCGAATGAAGCGGATGA pCas9g2-D15-GFP R106TCCACCACCGCTTTCCCAT R107 27A ATGAAATTGCTCATCGTCTCGTG R108ATGGCTCGAGCACCCAGG R109 28 GACAGCCGAATTCGGATTCC pCas9g1-D15-KinA, R110AAGCTTGCCATCTTAACCGGA pCas9g2- R111 28A GGATTCCCGCGTATATCTTGA D15-KinAR112 GATAAGGAGATCATTGAGGAAGC R113 29 GAACCTGCAAGCCCGGAATpCas9g1-D15-KinA, R114 TCGCAGTTTAGGGATTGATGG pCas9g2- R115 29AGGAATCGACTACATATATAACGG D15-KinA R116 GATGGCCTGTTTCTTCTTCAAG R117 30TTGTCAAGCAATCCTGGTTCAC pCas9g1-D15-KinA, R118 TCTCTTTTACATCCTCGTGATCGpCas9g2- R119 30A CCTTTCAGAACAGGGTCATCTA D15-KinA R120TCGCAAGGATGCAGCTGATC R121 31 ACCGAAGATGAGCATTCTGTTC pCas9g1-D15-KinA,R122 TATGATAATGTCTACTGTTCCCC pCas9g2- R123 31A GTTCATGTTACTGTCAAAGACGAD15-KinA R124 CCCATCAGGCATTGATTCAAC R125 32 ACATGTGGACAGCCATCCTGpCas9g1-D15-KinA, R126 ATGTATAACTCCCTGATGGTTTTC pCas9g2- R127 32AATCCTGAAAAAGGCACAGCGT D15-KinA R128 TGTCACCATTAATCCAAGCCC RR129 33GTCATAGCTGTTTCCTGTGTG pUC57 RR130 CAAGCTTGGCGTAATCATGGT RR131 33ATGTGTGAAATTGTTATCCGCTCA RR132 TGCAGAGGCCTGCATGCAA RR133 34CCGCTTACCGGATACCTGT pUC57 RR134 GAAGCTCCCTCGTGCGCT RR135 34ATGTCCGCCTTTCTCCCTTC RR136 CAGGCGTTTCCCCCTGGA RR137 35GAACGAAAACTCACGTTAAGGG pUC57 RR138 ACGGGGTCTGACGCTCAG RR139 35AGGGATTTTGGTCATGAGATTATC RR140 GGATCTCAAGAAGATCCTTTGAT RR141 36AGCGGTTAGCTCCTTCGGT pUC57 RR142 CCCAACGATCAAGGCGAGTT RR143 36AGGTCCTCCGATCGTTGTCA RR144 GGCTTCATTCAGCTCCGGTT RR145 37CACCTGACGTCTAAGAAACCAT pUC57 RR146 ACATTTCCCCGAAAAGTGCCA RR147 37AAGGCGTATCACGAGGCCC RR148 TAGGGGTTCCGCGCACATTT RR149 38GAAAGGGGGATGTGCTGCAA pUC57 RR150 CTTCGCTATTACGCCAGCTG RR151 38ATCGGTGCGGGCCTCTTC RR152 GCAAGGCGATTAAGTTGGGTA Targets labeled with an“A” (1A, 2A, 3A . . . ) correspond to nested PCRs, which are performedwhen increased specificity is needed. The sequences of oligo R001-oligoRR152 correspond to SEQ ID Nos: 73-224, respectively.

Bioengineered Spores: GFP Expressing Spores and Artificial Sporulation.

Spores of Bacillus can be bioengineered, primarily through theexpression of proteins and peptides on the spore coat.²⁸ Using ourplasmids that self-digest in the fore-spore, we explored the possibilityof expressing GFP on the coat of spores without altering their genome.To achieve this goal, we took advantage of a fusion protein (CotB-GFP)reported in a previous study, in which the spore coat protein CotB wasused to localize GFP on the spore coat.²⁹ We paired a CotB-GFPexpression cassette to our circuit for plasmid self-digestion (FIGS.20-21 , Supporting DNA Sequences) and produced spores. We examined thesespores through qPCR and PCR as described in the previous sections andfound that nearly 90% of them had no plasmid (Tables 1-2). We alsostudied these spores for green fluorescence through confocal microscopyand found that all expressed GFP on their coats (FIGS. 3A-3D, FIGS.24A-24D). Thus, while the majority of these spores have plasmidsself-digested, they are expressing GFP in their coats. Therefore, theseexperiments demonstrate the potential for engineering organisms withoutgenome alterations, while taking advantage of the customizability thatcomes with designer plasmids.

In a separate bioengineering example, we used the self-digestingplasmids containing a synthetic gene circuit to artificially inducesporulation. Previous findings showed that overexpression of KinA in B.subtilis can induce sporulation even in the absence of chemical orphysical sporulation inducers.³⁰ On the basis of this finding, we builta gene circuit to overexpress KinA for constitutive sporulation andassembled it together with the circuit for plasmid self-digestion (FIGS.22-23 , Supporting DNA Sequences).

Using the KinA circuit (pCas9g1-D15-KinA and pCas9g2-D15-KinA), we wereable to obtain spores in LB media with a sporulation yield comparable tothe original study³⁰ (Table 3). We found that approximately 90% of thespores produced with the KinA circuit had no detectable plasmid (Tables1 and 2).

TABLE 3 Sporulation Induction CFU/mL Plasmid Medium Viable cells SporesEfficiency no plasmid LB 8.3 × 10⁸ 1.1 × 10⁴ 1.3 × 10⁻⁵ DSM 5.0 × 10⁸4.1 × 10⁸ 8.2 × 10⁻¹ pBb LB 7.8 × 10⁸ 1.4 × 10⁴ 1.8 × 10⁻⁵ DSM 4.2 × 10⁸2.7 × 10⁸ 6.4 × 10⁻¹ pCas9g1-D15-KinA LB 3.0 × 10⁸ 1.2 × 10⁸ 4.0 × 10⁻¹DSM 1.9 × 10⁸ 0.8 × 10⁸ 4.2 × 10⁻¹ pCas9g2-D15-KinA LB 3.6 × 10⁸ 1.9 ×10⁸ 5.2 × 10⁻¹ DSM 2.2 × 10⁸ 1.3 × 10⁸ 5.9 × 10⁻¹

Besides qPCR and colony PCR, we analyzed spores of the strainpCas9g1-D15-KinA through atomic force microscopy and observed that theypossessed similar size, and similar morphology to wild type spores,characterized by wrinkles on the spore surface and overall sporedimensions (FIGS. 4A-4B). Thus, we were able to produce spores throughartificial sporulation, with the majority without detectible genomealterations, and these appeared to be morphologically similar to the WTspores.

Isolation and Sequencing of Plasmids Retained.

To better understand why the plasmid was retained in nearly 10% of thespores from strains pCas9g1-D15, pCas9g2-D15, and their derivatives, weisolated the retained plasmids (from strains germinated with LB) andanalyzed each plasmid by DNA sequencing. We detected that severalmutations emerged on DNA fragments that are key for the functioning ofthe self-digestion gene circuit such as the sequence being targeted byCas9, or the Cas9 gene itself (Table 4).

TABLE 4 Mutations in Retained Plasmids^(a) TS mutation TS truncated andcomplete Cas9 Plasmid Indels deletion gene pCas9g1-D15 6/11 3/11 2/11pCas9g1-D15-GFP 9/11 1/11 1/11 pCas9g1-D15-KinA 11/12  1/12 0/12pCas9g2-D15 8/8 0/8  0/8  pCas9g2-D15-GFP 11/12  1/12 0/12pCas9g2-D15-KinA 9/13 3/13 1/13 ^(a)Data represents the number ofplasmids of a species with mutations of a certain category over thetotal plasmids retained of that species.

To confirm whether mutations in the plasmids were responsible for thefailure of plasmid self-digestion, we used the isolated plasmids totransform wild type bacteria and performed sporulation. We analyzed thenewly generated spores by comparing germination on antibiotic-free mediavs media containing antibiotic and observed a similar amount of coloniesin both media (FIGS. 25A-25C). This resistance to antibiotic indicatesthat plasmid self-digestion did not occur, a result of the mutationsthat arose as shown in Table 4.

Several factors may have played a role for the mutations shown in Table4. In general, double-stranded breaks are known to be recognized by DNArepair and recombination machineries.³¹⁻³⁴ Additionally, CRISPR-Cassystems have also been reported to have interactions with DNA repairmachineries,³⁵⁻³⁸ although the precise mechanisms are not fullyunderstood. We also find in the literature that different enzymes playimportant roles on ensuring the integrity of the DNA before entry intosporulation. For example, Sda prevents entry into sporulation inresponse to DNA damage, or when there is only one copy of DNA, whichwould generate anucleate, unviable spores.³¹ SirA on the other hand,prevents that the chromosome copy number exceeds two.³¹ Distinctly, DisAdelays entry into sporulation if the chromosome is compromised by DNAdamage, although it is not clear if it has specificity for chromosomicDNA or if it can also affect plasmid DNA.³¹ Further understanding on howCas9 interacts with the diverse molecular pathways in B. subtilis duringsporulation could be a key factor to redesigning our strategy, whileemerging Cas9-based gene editing techniques continue to rely on therepair of double-stranded breaks by the host.^(35,39,40)

Our results show that it is possible to eliminate plasmids whileexpressing phenotypes in most of the spores. At the population level,approximately 90% of the spores produced with our approach were freefrom detectible plasmids and plasmid integration into the chromosome.While we identified mutations of the self-digestion circuitry andplasmid integration as impediments to make our plasmids fully disappearfrom the spore population, previous studies involving DNA digestion inthe bacteria E. coli show that it is possible to eliminate plasmids inan entire population.^(16,17) One of these studies used engineeredphages to infect bacteria and cause the elimination of native plasmidsthat provide antibiotic resistance,¹⁶ and another study used genecircuits inserted in the genome that can eliminate plasmids byinduction, as a strategy to protect industrial secrets contained in DNAsequences.¹⁷ One of the reasons behind the disparity in efficiency ofplasmid elimination in E. coli vs sporulating B. subtilis could be thedifferences in the bacterial host, for example, the activity of host DNArepair machineries and DNA exonucleases, and possible involvement ofunknown anti-CRISPR-Cas systems.⁴¹ A better understanding of thesemechanisms could help find ways to enhance plasmid elimination furtherin the spore system, which could benefit the use of bioengineeringconcepts in various applications without causing genetic alterations.

In contrast to the biocontainment approaches that lower the viability oforganisms in the natural environment, our approach to the bioengineeringof spores of Bacillus subtilis offers the possibility to releasebioengineered spores to the environment without introducing synthetic orforeign DNA sequences. This feature could be particularly useful in thecase of spores, because several spore-based industrial products areintended to be released to the environment, such as spore-basedbiopesticides that have long been used in the wild type form.⁴² Sporebioengineering could also benefit other applications of spores invaccines, probiotics, energy converting materials,⁴³ and living materialsystems. Remarkably, the only way to produce these spores is to use thesource bacteria that are transformed by the plasmid containing thesynthetic gene circuit. If the first generation of spores derived fromthis source germinates, subsequent generations of bacteria and thespores will not retain the bioengineered features of the firstgeneration of spores. This characteristic may provide advantages in thecommercialization of bioengineered spore technologies by preventing thereplication of the bioengineered features in the subsequent generationsof spores. Furthermore, if accidental germination degrades the functionof the spore-based products, the synthetic gene circuit couldpotentially be used to block the expression of key spore receptors tocause deficiency in germination.⁴⁴

Materials and Methods Strains, Media, and Plasmid Construction.

For cloning purposes, we used Mix & Go Z-competent E. coli strain Zymo5a from Zymo Research (cat. no. T3007). We used Gibson Assembly for theconstruction of the plasmids and confirmed the DNA sequence by Sangersequencing.

Transformation of B. subtilis 168 was performed through electroporationas previously described,⁴⁵ followed by growth at 37° C. on LB platescontaining 25 μg/mL chloramphenicol. We used plasmid pHY300PLK46 tobuild pBb, which we used as the backbone to build all our designerplasmids. Details for genetic constructions can be found in Table 5.Plasmid maps can be found in FIGS. 6-23 . Plasmid DNA sequences can befound in Supporting DNA Sequences. Several synthetic genetic parts shownin the plasmid maps were taken from a library of parts for B. subtilispreviously reported.⁴⁷

TABLE 5 Primers used for the construction of the plasmids in our studyOligo (SEQ Target Resulting ID No.) Oligo sequence (5′→3′) DNA Sourceplasmid 001 ttgtccttttccgctgcata pHY300PLK Takara Bio - pV1AACAATATGGCCCGTTTG #3060 002 gccagggttttcccagtcac TGCAGATCTCTAGAAGCT 003caagcttctagagatctgca pSEVA3b61 Addgene - GTGACTGGGAAAACCCT #58310 004aacaaacgggccatattgtt TATGCAGCGGAAAAGGAC 005 tatggaaaaacgctttgccc gB1Gene pV1RX CACACAGGCTCTTGAACAAG fragment 006 AACACCATTGACTCCTTCATCsynthesis 007 GCAGCCAAGTGAATACACTG gB2 Gene 008 Actgcagatctctagaagctfragment ATGCTGAATGACTTCTTACAGC synthesis 009 tgtaagaagtcattcagcat pV1This study AGCTTCTAGAGATCTGCA 010 cttgttcaagagcctgtgtg GGGCAAAGCGTTTTTCC011 tacggttatccacagaatca pV1RX This study pBb GAGGGCAAACTACTAGAGA 012ccaagtaatcgtgaatgtcg ACCGGATAAGGAGATCATTG 013 caatgatctccttatccggtpJWV102- Addgene - CGACATTCACGATTACTTGG PL-dCas9 #85588 014atctctagtagtttgccctc TGATTCTGTGGATAACCGTA 015 gcttgtcagggggcg gB20 GenepV1- GAGCCTATGGAAAAACGCTTTG fragment PsspA 016 ccctttaagagcgtcatgtasynthesis AACTTCATTGTAAATTCTGAAGAAATA CTTGTCAAG 017 tcagaatttacaatgaagttgB20 Gene TACATGACGCTCTTAAAGGGG fragment 018 tcgccagggttttc synthesisCCAGTCACTGCAGATCTCT 019 AGCTTCTAGAGATCTGCA pV1 This study 020GGGCAAAGCGTTTTTCC 021 AATAGGCTTAGATATCGGCACA pCas9 Addgene - pCas9g1-022 TCAGTCACCTCCTAGCTG #42876 cons 023 GAAACACGCATTGATTTGAGT pV1-This study 024 CCCATCCGACGCTATTTGT PsspA 025 gactggagcttctagagatc gB26Gene pCas9g2- AGGTCAGACGCGATTTCC fragment cons 026 gggttttcccagtcactgcasynthesis TGACCCAGACACCTATTCC 027 aggaataggtgtctgggtca pCas9g1-This study TGCAGTGACTGGGAAAACC cons 028 caggaaatcgcgtctgacctGATCTCTAGAAGCTCCAGTCAC 029 tacaatgaagtttacatgac gB27 Gene pCas9g1-GATTAACTAATAAGGAGGGCAAAC fragment D15-cons 030 ctaaaaccccctttaagagcsynthesis TTATCATTGTTCCGCGATCTC 031 agatcgcggaacaatgataa pCas9g1-This study GCTCTTAAAGGGGGTTTTAGA cons 032 gccctccttattagttaatcGTCATGTAAACTTCATTGTAAATTCTGA AG 033 tacaatgaagtttacatgac gB27 GenepCas9g2- GATTAACTAATAAGGAGGGCAAAC fragment D15-cons 034ctaaaaccccctttaagagc synthesis TTATCATTGTTCCGCGATCTC 035agatcgcggaacaatgataa pCas9g2- This study GCTCTTAAAGGGGGTTTTAGA consgccctccttattagttaatc 036 GTCATGTAAACTTCATTGTAAATTCTGA AG 037gttttggtccctcaatgatc gB27 Gene pCas9g1 TCCTTATCCGGTTAAGATGG fragment 038ttgtgccgatatcta synthesis AGCCTATTGAGTATTTCTTATCCAT 039ATGGATAAGAAATACTCAATAGGCT pCas9g1- This study 040 CCATCTTAACCGGATAAGGAcons 041 gttttggtccctcaatgatc gB27 Gene pCas9g2 TCCTTATCCGGTTAAGATGGfragment 042 ttgtgccgatatcta synthesis AGCCTATTGAGTATTTCTTATCCAT 043ATGGATAAGAAATACTCAATAGGCT pCas9g2- This study 044 CCATCTTAACCGGATAAGGAcons 045 gttttggtccctcaatgatc gB28 Gene pCas9g1- TCCTTATCCGGTTAAGATGGfragment D15 046 cctcttcctcctcgatgaat synthesis TTGCCCCAGGATTTACTCAT 047ATGAGTAAATCCTGGGGCAA pCas9g1- This study 048 CCATCTTAACCGGATAAGGAD15-cons 049 gttttggtccctcaatgatc gB28 Gene pCas9g2-TCCTTATCCGGTTAAGATGG fragment D15 050 cctcttcctcctcgatgaat synthesisTTGCCCCAGGATTTACTCAT 051 ATGAGTAAATCCTGGGGCAA pCas9g2- This study 052CCATCTTAACCGGATAAGGA D15-cons 053 ccttatccggttaagatggc pCas9g1-This study pCas9g1- GAGTAAATCCTGGGGCAAA D15 D15-mut 054atttgccccaggatttactc GCCATCTTAACCGGATAAGG 055 ccttatccggttaagatggcpCas9g2- This study pCas9g2- GAGTAAATCCTGGGGCAAA D15 D15-mut 056atttgccccaggatttactc GCCATCTTAACCGGATAAGG 057 gagcgtctcagcttctagagpCas9g1- This study pCas9g1- GTGACTGGGAAAACCCTG D15 D15-GFP 058cggataaggagatcattgag GAAGCTATACTGTAAAGTACAAGCA 059 gtactttacagtatagcttcgB21 Gene CTCAATGATCTCCTTATCCGG fragment 060 gccagggttttcccagtcacsynthesis CTCTAGAAGCTGAGACGCT 061 gagcgtctcagcttctagag pCas9g2-This study pCas9g2- TAGAGATCTGCAGTGACTGG D15 D15-GFP 062cggataaggagatcattgag GAAGCTATACTGTAAAGTACAAGCA 063 gtactttacagtatagcttcgB21 Gene CTCAATGATCTCCTTATCCGG fragment 064 ccagtcactgcagatctctasynthesis CTCTAGAAGCTGAGACGCT 065 ttaagatggcaagcttgaca B. subtilisRef. 30 pCas9g1- GCCGAATTCGGATTCCCG MF2352 D15-KinA 066ttgtaaagctcgtccatccc chromosome CGGGCATGCTTATTTTTTTGGA 067caaaaaaataagcatgcccg pCas9g1- This study GGGATGGACGAGCTTTAC D15-GFP 068cgcgggaatccgaattcggc TGTCAAGCTTGCCATCTTAAC 069 ttaagatggcaagcttgacaB. subtilis Ref. 30 pCas9g2- GCCGAATTCGGATTCCCG MF2352 D15-KinA 070ttgtaaagctcgtccatccc chromosome CGGGCATGCTTATTTTTTTGGA 071caaaaaaataagcatgcccg pCas9g2- This study GGGATGGACGAGCTTTAC D15-GFP 072cgcgggaatccgaattcggc TGTCAAGCTTGCCATCTTAAC Lowercases represent oligotails (for construction through Gibson Assembly)

Sporulation, Purification, and Determination of Sporulation Efficiency.

For sporulation, freshly transformed bacterial colonies were grown inshaking antibiotic-free LB for 2 h at 37° C. One volume of this culturewas then centrifuged and resuspended in 200 volumes of antibiotic-freeDSM and incubated for 3 h in shaking at 37° C. Finally, one volume ofthis culture was centrifuged and resuspended in 20 volumes ofantibiotic-free DSM and incubated for 24 h to let cells sporulate.

Spore purification was carried out following two different methods.Method 1: Spores were collected by centrifugation, resuspended inresuspension buffer (50 mM Tris, 50 mg/L lysozyme, pH 7.5), centrifuged,washed with 0.05% SDS, and then centrifuged and washed with doubledistilled water (ddH2O) three times. Method 2: Spores were treated as inMethod 1 followed by centrifugation and resuspension in 0.5% sodiumhypochlorite for 10 min at room temperature. Immediately after 10 min, 3volumes of 5 mg/L sodium thiosulfate were added and the sample wasshortly vortexed. The resulting sample was washed twice with ddH2O andthen treated with DNase I at 37° C. followed by heat inactivation at 75°C. The resulting sample was washed with ddH2O twice.

Spores obtained by artificial sporulation induction were purifiedthrough Method 1, and sporulation efficiency was determined aspreviously reported in the literature.⁴⁸ GFP spores were purified usingMethod 1, omitting the SDS step. Spores for qPCR, spores that were latergerminated for colony PCR, and spores used for the antibiotic-basedplate assay were purified through Method 2.

qPCR-Based Assay for Plasmid Quantification.

Spores obtained with the purification Method 2 were lysed using theOmniLyse Cell Lysis Kit (Claremont Biosolutions, LLC. cat. no.01.341.24) for 60 seconds in the static mode. The resulting sample wasused for absolute quantification of plasmid through qPCR following amethod previously reported.⁴⁹ We used primers QPCRCH1

(5′-ACTGCCCGTTACTGGTATAAAG-3′; SEQ ID No: 243)

and QPCRCH2

(5′-TGCACCTTGCTTTGGTTTATG-3′; SEQ ID No: 244)to target the chromosome, and primers QPCRP1(5′-GGCGGTGATCACTGATGAATA-3′; SEQ ID No: 245) and QPCRP2(5′-GCTGTCTCTCCACTGTCAAATA-3′; SEQ ID No: 246) to target a conservedsequence among all the plasmids used in our study. Neither of the twodifferent sets of primers amplified the opposite target.

Colony PCR-Based Assay for Plasmid Detection.

Spores obtained with purification Method 2 were plated on LB-agarwithout antibiotic after having being diluted such that every resultingcolony would be the product of a single spore. Full colonies were pickedand resuspended with water individually. Colonies were analyzed throughcolony PCR with primers targeting the plasmid. Amplification or noamplification was counted as the presence or absence of plasmid,correspondingly. One hundred colonies were analyzed for every strain.

Antibiotic-Based Assay for Plasmid Detection.

Spores obtained by purification Method 2 were plated on LB-agar with orwithout antibiotic.

Isolation of Plasmid after Sporulation, and Sequencing.

We used the QIAprep Spin Miniprep Kit from QIAGEN to isolate plasmid DNAfrom B. subtilis. In addition to the protocol of the manufacturer, weadded 1 mg/mL lysozyme in the step in which a bacteria pellet isresuspended with buffer P1. This bacterial resuspension was incubated at37° C. for 10 min. After that, we followed the protocol of themanufacturer.

GFP-Coated Spores.

GFP-coated spores were obtained with purification Method 1 (skipping theuse of 0.05% SDS), placed on a glass bottom dish, and dried byevaporation through incubation at room temperature overnight. A ZeissLSM 800 microscope was used for confocal microscopy using the 63×objective. GFP was excited with a laser at 488 nm, and its emission wasdetected in the range of 500-520 nm. Because autofluorescence has beenpreviously observed in wild type spores in long periods of GFPexcitation,²⁹ we limited exposure time to 2-5 s.

Atomic Force Microscopy.

Atomic force microscopy was carried out with a multimode SPM (VeecoInstruments) operated in tapping mode as previously described.⁵⁰

Detection of Plasmid Integration into the Chromosome.

The detection of plasmid integration events was performed in accordanceto a previously described protocol known as inverse PCR.⁵¹ Genomic DNAof B. subtilis was extracted and treated with restriction enzyme CviQIor DpnII to produce fragments of about 3000 bp or less. Then, DNAfragments were religated with T4 ligase, and used for PCR. A second,nested PCR was performed, and amplified DNA fragments were sequenced.Several sets of primers were used to target different locations alongthe plasmids (Table 7). Integration was confirmed or discarded byalignment of the sequenced DNA against the genome of B. subtilis strain168, using the tool blastn from the NCBI.

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Supporting DNA Sequences

>pV1 (SEQ ID No: 225) ttgtccttttccgctgcataaacaatatggcccgtttgttGAACTACTCTTTAATAAAATAATTTTTCCGTTCCCAATTCCACATTGCAATAATAGAAAATCCATCTTCATCGGCTTTTTCGTCATCATCTGTATGAATCAAATCGCCTTCTTCTGTGTCATCAAGGTTTAATTTTTTATGTATTTCTTTTAACAAACCACCATAGGAGATTAACCTTTTACGGTGTAAACCTTCCTCCAAATCAGACAAACGTTTCAAATTCTTTTCTTCATCATCGGTCATAAAATCCGTATCCTTTACAGGATATTTTGCAGTTTCGTCAATTGCCGATTGTATATCCGATTTATATTTATTTTTCGGTCGAATCATTTGAACTTTTACATTTGGATCATAGTCTAATTTCATTGCCTTTTTCCAAAATTGAATCCATTGTTTTTGATTCACGTAGTTTTCTGTATTCTTAAAATAAGTTGGTTCCACACATACCAATACATGCATGTGCTGATTATAAGAATTATCTTTATTATTTATTGTCACTTCCGTTGCACGCATAAAACCAACAAGATTTTTATTAATTTTTTTATATTGCATCATTCGGCGAAATCCTTGAGCCATATCTGACAAACTCTTATTTAATTCTTCGCCATCATAAACATTTTTAACTGTTAATGTGAGAAACAACCAACGAACTGTTGGCTTTTGTTTAATAACTTCAGCAACAACCTTTTGTGACTGAATGCCATGTTTCATTGCTCTCCTCCAGTTGCACATTGGACAAAGCCTGGATTTACAAAACCACACTCGATACAACTTTCTTTCGCCTGTTTCACGATTTTGTTTATACTCTAATATTTCAGCACAATCTTTTACTCTTTCAGCCTTTTTAAATTCAAGAATATGCAGAAGTTCAAAGTAATCAACATTAGCGATTTTCTTTTCTCTCCATGGTCTCACTTTTCCACTTTTTGTCTTGTCCACTAAAACCCTTGATTTTTCATCTGAATAAATGCTACTATTAGGACACATAATATTAAAAGAAACCCCCATCTATTTAGTTATTTGTTTGGTCACTTATAACTTTAACAGATGGGGTTTTTCTGTGCAACCAATTTTAAGGGTTTTCCAATACTTTAAAACACATACATACCAACACTTCAACGCACCTTTCAGCAACTAAAATAAAAATGACGTTATTTCTATATGTATCAAGATAAGAAAGAACAAGTTCAAAACCATCAAAAAAAGACACCTTTTCAGGTGCTTTTTTTATTTTATAAACTCATTCCCTGATCTCGACTTCGTTCTTTTTTTACCTCTCGGTTATGAGTTAGTTCAAATTCGTTCTTTTTAGGTTCTAAATCGTGTTTTTCTTGGAATTGTGCTGTTTTATCCTTTACCTTGTCTACAAACCCCTTAAAAACGTTTTTAAAGGCTTTTAAGCGTCTGTACGTTCCTTAAGGAATTATTCCTTAGTGCTTTCTAGGTTAATGTCATGATAATAATGGTTTCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTCCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTGTTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGCAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCTTAATAAGATGATCTTCTTGAGATCGTTTTGGTCTGCGCGTAATCTCTTGCTCTGAAAACGAAAAAACCGCCTTGCAGGGAGGTTTTTCGAAGGTTCTCTGAGCTACCAACTCTTTGAACCGAGGTAACTGGCTTGCAGGAGCGCAGTCACCAAAACTTGTCCTTTCAGTTTAGCCTTAACCGGCGCATGACTTCAAGACTAACTCCTCTAAATCAATTACCAGTGGCTGCTGCCAGTGGTGCTTTTGCATGTCTTTCCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGACTGAACGGGGGGTTCGTGCATACAGTCCAGCTTGGAGCGAACTGCCTACCCGGAACTGAGTGTCAGGCGTGGAATGAGACAAACGCGGCCATAACAGCGGAATGACACCGGTAAACCGAAAGGCAGGAACAGGAGAGCGCACGAGGGAGCCGCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCACTGATTTGAGCGTCAGATTTCGTGATGCTTGTCAGGGGGCGGAGCCTATGGAAAAACGCTTTGCCcaagcttctagagatctgcagtgactgggaaaaccctggcGACTAGTCTTGGACTCCTGTTGATAGATCCAGTAATGACCTCAGAACTCCATCTGGATTTGTTCAGAACGCTCGGTTGCCGCCGGGCGTTTTTTATTGGTGAGAATCCAGGGGTCCCCAATAATTACGATTTAAATCCTTCAAACTTCCCAAAGGCGAGCCCTAGTGACATTAGAAAACCGACTGTAAAAAGTACAGTCGGCATTATCTCATATTATAAAAGCCAGTCATTAGGCCTATCTGACAATTCCTGAATAGAGTTCATAAACAATCCTGCATGATAACCATCACAAACAGAATGATGTACCTGTAAAGATAGCGGTAAATATATTGAATTACCTTTATTAATGAATTTTCCTGCTGTAATAATGGGTAGAAGGTAATTACTATTATTATTGATATTTAAGTTAAACCCAGTAAATGAAGTCCATGGAATAATAGAAAGAGAAAAAGCATTTTCAGGTATAGGTGTTTTGGGAAACAATTTCCCCGAACCATTATATTTCTCTACATCAGAAAGGTATAAATCATAAAACTCTTTGAAGTCATTCTTTACAGGAGTCCAAATACCAGAGAATGTTTTAGATACACCATCAAAAATTGTATAAAGTGGCTCTAACTTATCCCAATAACCTAACTCTCCGTCGCTATTGTAACCAGTTCTAAAAGCTGTATTTGAGTTTATCACCCTTGTCACTAAGAAAATAAATGCAGGGTAAAATTTATATCCTTCTTGTTTTATGTTTCGGTATAAAACACTAATATCAATTTCTGTGGTTATACTAAAAGTCGTTTGTTGGTTCAAATAATGATTAAATATCTCTTTTCTCTTCCAATTGTCTAAATCAATTTTATTAAAGTTCATTTGATATGCCTCCTAAATTTTTATCTAAAGTGAATTTAGGAGGCTTACTTGTCTGCTTTCTTCATTAGAATCAATCCTTTTTTAAAAGTCAATCCCGTTTGTTGAAGACTT >pV1RX (SEQ ID No: 226)tatggaaaaacgctttgccccacacaggctcttgaacaagGGATAACAATTTGTCATAGCTGTATTCGTTACAAGGAGGATTTTCGAAAAAACACCCTAACGGGTGTTTTTTTATAGCTGGTCTCCCTTGCTTGTACTTTACAGTATGCCATACGAAACTGCGTCAATACACGTTGACACTCTTTTGTAGTTATGTTAAATTATCAGATCGCCATCATTAGTTTGTTTAAACAACAAACTAATACTAGAGGCTCTTAAAGGGGGTTTTAGATACCAGAGATGGTGAGCAAGGGCGAGGAGGATAACATGGCCATCATCAAGGAGTTCATGCGCTTCAAGGTGCACATGGAGGGCTCCGTGAACGGCCACGAGTTCGAGATCGAGGGCGAGGGCGAGGGCCGCCCCTACGAGGGCACCCAGACCGCCAAGCTGAAGGTGACCAAGGGTGGCCCCCTGCCCTTCGCCTGGGACATCCTGTCCCCTCAGTTCATGTACGGCTCCAAGGCCTACGTGAAGCACCCCGCCGACATCCCCGACTACTTGAAGCTGTCCTTCCCCGAGGGCTTCAAGTGGGAGCGCGTGATGAACTTCGAGGACGGCGGCGTGGTGACCGTGACCCAGGACTCCTCCCTGCAGGACGGCGAGTTCATCTACAAGGTGAAGCTGCGCGGCACCAACTTCCCCTCCGACGGCCCCGTAATGCAGAAGAAGACCATGGGCTGGGAGGCCTCCTCCGAGCGGATGTACCCCGAGGACGGCGCCCTGAAGGGCGAGATCAAGCAGAGGCTGAAGCTGAAGGACGGCGGCCACTACGACGCTGAGGTCAAGACCACCTACAAGGCCAAGAAGCCCGTGCAGCTGCCCGGCGCCTACAACGTCAACATCAAGTTGGACATCACCTCCCACAACGAGGACTACACCATCGTGGAACAGTACGAACGCGCCGAGGGCCGCCACTCCACCGGCGGCATGGACGAGCTGTACAAGTAATAGCTGCCACCTTTCTGAACTTTGGTAATGCGTCTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCCTCAATGATCTCCTTATCCGGTTAAGATGGCAAGCTTGACAAGTATTTCTTCAGAATTTACAATGAAGTTTACTAGAGGATTAACTAATAAGGAGGGCAAACTACTAGAGATGACGGGCCTGAACAAGAGCACCGTAAgcagccaagtgaat acactgatgaaggagtcaatggtgttCGAGATCGGCCAGGGCCAGAGCTCAGGTGGCCGCCGCCCGGTAATGTTAGTCTTCAACAAGAAAGCGGGCTATAGTGTGGGCATCGACGTCGGCGTAGACTACATCAACGGAATCCTTACGGATTTAGAGGGCACGATTGTGTTGGACCAGTATAGACACCTTGAGAGCAACAGCCCGGAGATCACTAAGGATATCCTTATCGACATGATCCACCATTTCATCACACAGATGCCTCAGAGCCCTTATGGATTCATCGGCATCGGCATCTGTGTACCGGGTTTAATCGACAAGGACCAGAAGATCGTGTTTACGCCTAATAGCAATTGGCGTGACATCGATCTGAAGAGCAGCATCCAGGAGAAATATAACGTAAGCGTGTTCATCGAGAACGAAGCGAACGCAGGAGCGTACGGCGAGAAGTTGTTCGGTGCAGCGAAGAACCATGACAATATCATCTATGTGTCAATTTCAACGGGCATCGGAATTGGCGTGATCATTAATAACCACCTGTACCGTGGCGTGTCAGGATTTAGCGGTGAGATGGGCCACATGACGATCGATTTCAACGGACCGAAGTGTTCATGTGGCAATAGAGGCTGTTGGGAGCTTTACGCGAGCGAGAAAGCGCTGCTGAAGAGCTTGCAAACGAAGGAGAAGAAACTCAGCTACCAGGACATCATCAATCTTGCACACCTTAACGACATTGGCACACTGAACGCGCTGCAGAACTTCGGCTTCTACCTGGGCATCGGATTGACAAACATCTTGAACACGTTCAATCCGCAGGCAGTGATCCTGCGCAACTCAATCATCGAGAGCCACCCGATGGTGCTGAACAGCATGCGCTCAGAGGTGAGCAGCCGTGTGTACAGCCAGCTCGGAAACTCATACGAGCTGCTTCCGAGCAGTCTTGGCCAGAACGCTCCTGCGCTTGGCATGAGCAGCATCGTAATCGACCACTTCTTAGATATGATCACGATGTAATAGTCAAATGTCAGACGAAAATGCCAATTATTGAAGCGGCTAACGCCGCTTTTTTTGTTTCTGGTCTCCCCATAGTTTAACAAGTGCtgtaagaagtcattcagcatagcttctagagatctgcagtGACTGGGAAAACCCTGGCGACTAGTCTTGGACTCCTGTTGATAGATCCAGTAATGACCTCAGAACTCCATCTGGATTTGTTCAGAACGCTCGGTTGCCGCCGGGCGTTTTTTATTGGTGAGAATCCAGGGGTCCCCAATAATTACGATTTAAATCCTTCAAACTTCCCAAAGGCGAGCCCTAGTGACATTAGAAAACCGACTGTAAAAAGTACAGTCGGCATTATCTCATATTATAAAAGCCAGTCATTAGGCCTATCTGACAATTCCTGAATAGAGTTCATAAACAATCCTGCATGATAACCATCACAAACAGAATGATGTACCTGTAAAGATAGCGGTAAATATATTGAATTACCTTTATTAATGAATTTTCCTGCTGTAATAATGGGTAGAAGGTAATTACTATTATTATTGATATTTAAGTTAAACCCAGTAAATGAAGTCCATGGAATAATAGAAAGAGAAAAAGCATTTTCAGGTATAGGTGTTTTGGGAAACAATTTCCCCGAACCATTATATTTCTCTACATCAGAAAGGTATAAATCATAAAACTCTTTGAAGTCATTCTTTACAGGAGTCCAAATACCAGAGAATGTTTTAGATACACCATCAAAAATTGTATAAAGTGGCTCTAACTTATCCCAATAACCTAACTCTCCGTCGCTATTGTAACCAGTTCTAAAAGCTGTATTTGAGTTTATCACCCTTGTCACTAAGAAAATAAATGCAGGGTAAAATTTATATCCTTCTTGTTTTATGTTTCGGTATAAAACACTAATATCAATTTCTGTGGTTATACTAAAAGTCGTTTGTTGGTTCAAATAATGATTAAATATCTCTTTTCTCTTCCAATTGTCTAAATCAATTTTATTAAAGTTCATTTGATATGCCTCCTAAATTTTTATCTAAAGTGAATTTAGGAGGCTTACTTGTCTGCTTTCTTCATTAGAATCAATCCTTTTTTAAAAGTCAATCCCGTTTGTTGAAGACTTTTGTCCTTTTCCGCTGCATAAACAATATGGCCCGTTTGTTGAACTACTCTTTAATAAAATAATTTTTCCGTTCCCAATTCCACATTGCAATAATAGAAAATCCATCTTCATCGGCTTTTTCGTCATCATCTGTATGAATCAAATCGCCTTCTTCTGTGTCATCAAGGTTTAATTTTTTATGTATTTCTTTTAACAAACCACCATAGGAGATTAACCTTTTACGGTGTAAACCTTCCTCCAAATCAGACAAACGTTTCAAATTCTTTTCTTCATCATCGGTCATAAAATCCGTATCCTTTACAGGATATTTTGCAGTTTCGTCAATTGCCGATTGTATATCCGATTTATATTTATTTTTCGGTCGAATCATTTGAACTTTTACATTTGGATCATAGTCTAATTTCATTGCCTTTTTCCAAAATTGAATCCATTGTTTTTGATTCACGTAGTTTTCTGTATTCTTAAAATAAGTTGGTTCCACACATACCAATACATGCATGTGCTGATTATAAGAATTATCTTTATTATTTATTGTCACTTCCGTTGCACGCATAAAACCAACAAGATTTTTATTAATTTTTTTATATTGCATCATTCGGCGAAATCCTTGAGCCATATCTGACAAACTCTTATTTAATTCTTCGCCATCATAAACATTTTTAACTGTTAATGTGAGAAACAACCAACGAACTGTTGGCTTTTGTTTAATAACTTCAGCAACAACCTTTTGTGACTGAATGCCATGTTTCATTGCTCTCCTCCAGTTGCACATTGGACAAAGCCTGGATTTACAAAACCACACTCGATACAACTTTCTTTCGCCTGTTTCACGATTTTGTTTATACTCTAATATTTCAGCACAATCTTTTACTCTTTCAGCCTTTTTAAATTCAAGAATATGCAGAAGTTCAAAGTAATCAACATTAGCGATTTTCTTTTCTCTCCATGGTCTCACTTTTCCACTTTTTGTCTTGTCCACTAAAACCCTTGATTTTTCATCTGAATAAATGCTACTATTAGGACACATAATATTAAAAGAAACCCCCATCTATTTAGTTATTTGTTTGGTCACTTATAACTTTAACAGATGGGGTTTTTCTGTGCAACCAATTTTAAGGGTTTTCCAATACTTTAAAACACATACATACCAACACTTCAACGCACCTTTCAGCAACTAAAATAAAAATGACGTTATTTCTATATGTATCAAGATAAGAAAGAACAAGTTCAAAACCATCAAAAAAAGACACCTTTTCAGGTGCTTTTTTTATTTTATAAACTCATTCCCTGATCTCGACTTCGTTCTTTTTTTACCTCTCGGTTATGAGTTAGTTCAAATTCGTTCTTTTTAGGTTCTAAATCGTGTTTTTCTTGGAATTGTGCTGTTTTATCCTTTACCTTGTCTACAAACCCCTTAAAAACGTTTTTAAAGGCTTTTAAGCGTCTGTACGTTCCTTAAGGAATTATTCCTTAGTGCTTTCTAGGTTAATGTCATGATAATAATGGTTTCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTCCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTGTTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGCAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCTTAATAAGATGATCTTCTTGAGATCGTTTTGGTCTGCGCGTAATCTCTTGCTCTGAAAACGAAAAAACCGCCTTGCAGGGAGGTTTTTCGAAGGTTCTCTGAGCTACCAACTCTTTGAACCGAGGTAACTGGCTTGCAGGAGCGCAGTCACCAAAACTTGTCCTTTCAGTTTAGCCTTAACCGGCGCATGACTTCAAGACTAACTCCTCTAAATCAATTACCAGTGGCTGCTGCCAGTGGTGCTTTTGCATGTCTTTCCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGACTGAACGGGGGGTTCGTGCATACAGTCCAGCTTGGAGCGAACTGCCTACCCGGAACTGAGTGTCAGGCGTGGAATGAGACAAACGCGGCCATAACAGCGGAATGACACCGGTAAACCGAAAGGCAGGAACAGGAGAGCGCACGAGGGAGCCGCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCACTGATTTGAGCGTCAGATTTCGTGATGCTTGTCAGGGGGCGGAGCC >pBb (SEQ ID No: 227)tacggttatccacagaatcagagggcaaactactagagat GACGGGCCTGAACAAGAGCACCGTAAGCAGCCAAGTGAATACACTGATGAAGGAGTCAATGGTGTTCGAGATCGGCCAGGGCCAGAGCTCAGGTGGCCGCCGCCCGGTAATGTTAGTCTTCAACAAGAAAGCGGGCTATAGTGTGGGCATCGACGTCGGCGTAGACTACATCAACGGAATCCTTACGGATTTAGAGGGCACGATTGTGTTGGACCAGTATAGACACCTTGAGAGCAACAGCCCGGAGATCACTAAGGATATCCTTATCGACATGATCCACCATTTCATCACACAGATGCCTCAGAGCCCTTATGGATTCATCGGCATCGGCATCTGTGTACCGGGTTTAATCGACAAGGACCAGAAGATCGTGTTTACGCCTAATAGCAATTGGCGTGACATCGATCTGAAGAGCAGCATCCAGGAGAAATATAACGTAAGCGTGTTCATCGAGAACGAAGCGAACGCAGGAGCGTACGGCGAGAAGTTGTTCGGTGCAGCGAAGAACCATGACAATATCATCTATGTGTCAATTTCAACGGGCATCGGAATTGGCGTGATCATTAATAACCACCTGTACCGTGGCGTGTCAGGATTTAGCGGTGAGATGGGCCACATGACGATCGATTTCAACGGACCGAAGTGTTCATGTGGCAATAGAGGCTGTTGGGAGCTTTACGCGAGCGAGAAAGCGCTGCTGAAGAGCTTGCAAACGAAGGAGAAGAAACTCAGCTACCAGGACATCATCAATCTTGCACACCTTAACGACATTGGCACACTGAACGCGCTGCAGAACTTCGGCTTCTACCTGGGCATCGGATTGACAAACATCTTGAACACGTTCAATCCGCAGGCAGTGATCCTGCGCAACTCAATCATCGAGAGCCACCCGATGGTGCTGAACAGCATGCGCTCAGAGGTGAGCAGCCGTGTGTACAGCCAGCTCGGAAACTCATACGAGCTGCTTCCGAGCAGTCTTGGCCAGAACGCTCCTGCGCTTGGCATGAGCAGCATCGTAATCGACCACTTCTTAGATATGATCACGATGTAATAGTCAAATGTCAGACGAAAATGCCAATTATTGAAGCGGCTAACGCCGCTTTTTTTGTTTCTGGTCTCCCCATAGTTTAACAAGTGCTGTAAGAAGTCATTCAGCATAGCTTCTAGAGATCTGCAGTGACTGGGAAAACCCTGGCGACTAGTCTTGGACTCCTGTTGATAGATCCAGTAATGACCTCAGAACTCCATCTGGATTTGTTCAGAACGCTCGGTTGCCGCCGGGCGTTTTTTATTGGTGAGAATCCAGGGGTCCCCAATAATTACGATTTAAATCCTTCAAACTTCCCAAAGGCGAGCCCTAGTGACATTAGAAAACCGACTGTAAAAAGTACAGTCGGCATTATCTCATATTATAAAAGCCAGTCATTAGGCCTATCTGACAATTCCTGAATAGAGTTCATAAACAATCCTGCATGATAACCATCACAAACAGAATGATGTACCTGTAAAGATAGCGGTAAATATATTGAATTACCTTTATTAATGAATTTTCCTGCTGTAATAATGGGTAGAAGGTAATTACTATTATTATTGATATTTAAGTTAAACCCAGTAAATGAAGTCCATGGAATAATAGAAAGAGAAAAAGCATTTTCAGGTATAGGTGTTTTGGGAAACAATTTCCCCGAACCATTATATTTCTCTACATCAGAAAGGTATAAATCATAAAACTCTTTGAAGTCATTCTTTACAGGAGTCCAAATACCAGAGAATGTTTTAGATACACCATCAAAAATTGTATAAAGTGGCTCTAACTTATCCCAATAACCTAACTCTCCGTCGCTATTGTAACCAGTTCTAAAAGCTGTATTTGAGTTTATCACCCTTGTCACTAAGAAAATAAATGCAGGGTAAAATTTATATCCTTCTTGTTTTATGTTTCGGTATAAAACACTAATATCAATTTCTGTGGTTATACTAAAAGTCGTTTGTTGGTTCAAATAATGATTAAATATCTCTTTTCTCTTCCAATTGTCTAAATCAATTTTATTAAAGTTCATTTGATATGCCTCCTAAATTTTTATCTAAAGTGAATTTAGGAGGCTTACTTGTCTGCTTTCTTCATTAGAATCAATCCTTTTTTAAAAGTCAATCCCGTTTGTTGAAGACTTTTGTCCTTTTCCGCTGCATAAACAATATGGCCCGTTTGTTGAACTACTCTTTAATAAAATAATTTTTCCGTTCCCAATTCCACATTGCAATAATAGAAAATCCATCTTCATCGGCTTTTTCGTCATCATCTGTATGAATCAAATCGCCTTCTTCTGTGTCATCAAGGTTTAATTTTTTATGTATTTCTTTTAACAAACCACCATAGGAGATTAACCTTTTACGGTGTAAACCTTCCTCCAAATCAGACAAACGTTTCAAATTCTTTTCTTCATCATCGGTCATAAAATCCGTATCCTTTACAGGATATTTTGCAGTTTCGTCAATTGCCGATTGTATATCCGATTTATATTTATTTTTCGGTCGAATCATTTGAACTTTTACATTTGGATCATAGTCTAATTTCATTGCCTTTTTCCAAAATTGAATCCATTGTTTTTGATTCACGTAGTTTTCTGTATTCTTAAAATAAGTTGGTTCCACACATACCAATACATGCATGTGCTGATTATAAGAATTATCTTTATTATTTATTGTCACTTCCGTTGCACGCATAAAACCAACAAGATTTTTATTAATTTTTTTATATTGCATCATTCGGCGAAATCCTTGAGCCATATCTGACAAACTCTTATTTAATTCTTCGCCATCATAAACATTTTTAACTGTTAATGTGAGAAACAACCAACGAACTGTTGGCTTTTGTTTAATAACTTCAGCAACAACCTTTTGTGACTGAATGCCATGTTTCATTGCTCTCCTCCAGTTGCACATTGGACAAAGCCTGGATTTACAAAACCACACTCGATACAACTTTCTTTCGCCTGTTTCACGATTTTGTTTATACTCTAATATTTCAGCACAATCTTTTACTCTTTCAGCCTTTTTAAATTCAAGAATATGCAGAAGTTCAAAGTAATCAACATTAGCGATTTTCTTTTCTCTCCATGGTCTCACTTTTCCACTTTTTGTCTTGTCCACTAAAACCCTTGATTTTTCATCTGAATAAATGCTACTATTAGGACACATAATATTAAAAGAAACCCCCATCTATTTAGTTATTTGTTTGGTCACTTATAACTTTAACAGATGGGGTTTTTCTGTGCAACCAATTTTAAGGGTTTTCCAATACTTTAAAACACATACATACCAACACTTCAACGCACCTTTCAGCAACTAAAATAAAAATGACGTTATTTCTATATGTATCAAGATAAGAAAGAACAAGTTCAAAACCATCAAAAAAAGACACCTTTTCAGGTGCTTTTTTTATTTTATAAACTCATTCCCTGATCTCGACTTCGTTCTTTTTTTACCTCTCGGTTATGAGTTAGTTCAAATTCGTTCTTTTTAGGTTCTAAATCGTGTTTTTCTTGGAATTGTGCTGTTTTATCCTTTACCTTGTCTACAAACCCCTTAAAAACGTTTTTAAAGGCTTTTAAGCGTCTGTACGTTCCTTAAGGAATTATTCCTTAGTGCTTTCTAGGTTAATGTCATGATAATAATGGTTTCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTCCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTGTTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGCAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCTTAATAAGATGATCTTCTTGAGATCGTTTTGGTCTGCGCGTAATCTCTTGCTCTGAAAACGAAAAAACCGCCTTGCAGGGAGGTTTTTCGAAGGTTCTCTGAGCTACCAACTCTTTGAACCGAGGTAACTGGCTTGCAGGAGCGCAGTCACCAAAACTTGTCCTTTCAGTTTAGCCTTAACCGGCGCATGACTTCAAGACTAACTCCTCTAAATCAATTACCAGTGGCTGCTGCCAGTGGTGCTTTTGCATGTCTTTCCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGACTGAACGGGGGGTTCGTGCATACAGTCCAGCTTGGAGCGAACTGCCTACCCGGAACTGAGTGTCAGGCGTGGAATGAGACAAACGCGGCCATAACAGCGGAATGACACCGGTAAACCGAAAGGCAGGAACAGGAGAGCGCACGAGGGAGCCGCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCACTGATTTGAGCGTCAGATTTCGTGATGCTTGTCAGGGGGCGGAGCCTATGGAAAAACGCTTTGCCCCACACAGGCTCTTGAACAAGGGATAACAATTTGTCATAGCTGTATTCGTTACAAGGAGGATTTTCGAAAAAACACCCTAACGGGTGTTTTTTTATAGCTGGTCTCCCTTGCTTGTACTTTACAGTATGCCATACGAAACTGCGTCAATACACGTTGACACTCTTTTGTAGTTATGTTAAATTATCAGATCGCCATCATTAGTTTGTTTAAACAACAAACTAATACTAGAGGCTCTTAAAGGGGGTTTTAGATACCAGAGATGGTGAGCAAGGGCGAGGAGGATAACATGGCCATCATCAAGGAGTTCATGCGCTTCAAGGTGCACATGGAGGGCTCCGTGAACGGCCACGAGTTCGAGATCGAGGGCGAGGGCGAGGGCCGCCCCTACGAGGGCACCCAGACCGCCAAGCTGAAGGTGACCAAGGGTGGCCCCCTGCCCTTCGCCTGGGACATCCTGTCCCCTCAGTTCATGTACGGCTCCAAGGCCTACGTGAAGCACCCCGCCGACATCCCCGACTACTTGAAGCTGTCCTTCCCCGAGGGCTTCAAGTGGGAGCGCGTGATGAACTTCGAGGACGGCGGCGTGGTGACCGTGACCCAGGACTCCTCCCTGCAGGACGGCGAGTTCATCTACAAGGTGAAGCTGCGCGGCACCAACTTCCCCTCCGACGGCCCCGTAATGCAGAAGAAGACCATGGGCTGGGAGGCCTCCTCCGAGCGGATGTACCCCGAGGACGGCGCCCTGAAGGGCGAGATCAAGCAGAGGCTGAAGCTGAAGGACGGCGGCCACTACGACGCTGAGGTCAAGACCACCTACAAGGCCAAGAAGCCCGTGCAGCTGCCCGGCGCCTACAACGTCAACATCAAGTTGGACATCACCTCCCACAACGAGGACTACACCATCGTGGAACAGTACGAACGCGCCGAGGGCCGCCACTCCACCGGCGGCATGGACGAGCTGTACAAGTAATAGCTGCCACCTTTCTGAACTTTGGTAATGCGTCTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCCTCcaatgatctccttatccggtcgacattcacgattacttggCTAGCGCTATATGCGTTGATGCAATTTCTATGCGCACCCGTTCTCGGAGCACTGTCCGACCGCTTTGGCCGCCGCCCAGTCCTGCTCGCTTCGCTACTTGGAGCCACTATCGACTACGCGATCATGGCGACCACACCCGTCCTGTGGATCTATCGATGCATGCAGCCGGTACCATCACAAGCACTTTGGGACGTTCTCCCTTAGTGCTTTTTTGATTTCTCATAGGCCGGCCTGTTAGTCATATGGACACTTAAGCTCTAGACGGTGATCAACACGCTAGCCAGGCATCAAATAAAACGAAAGGCTCAGTCGAAAGACTGGGCCTTTCGTTTTATCTGTTGTTTGTCGGTGAACGCTCTCTACTAGAGTCACACTGGCTCACCTTCGGGTGGGCCTTTCTGCGTTTATAGAATTCACTAGTAATTGTGAGGCGGATAACAATTCTCACTCATTCTACAGTTTATTCTTGACATTGCACTGTCCCCCTGGTATAATAACTAATTGTGAGCGCTCACAATTAAGATCCCCGGGGCGGCCGCGAATTCAAAAGATCTAAAGAGGAGAAAGGATCTATGGATAAGAAATACTCAATAGGCTTAGCTATCGGCACAAATAGCGTCGGATGGGCGGTGATCACTGATGAATATAAGGTTCCGTCTAAAAAGTTCAAGGTTCTGGGAAATACAGACCGCCACAGTATCAAAAAAAATCTTATAGGGGCTCTTTTATTTGACAGTGGAGAGACAGCGGAAGCGACTCGTCTCAAACGGACAGCTCGTAGAAGGTATACACGTCGGAAGAATCGTATTTGTTATCTACAGGAGATTTTTTCAAATGAGATGGCGAAAGTAGATGATAGTTTCTTTCATCGACTTGAAGAGTCTTTTTTGGTGGAAGAAGACAAGAAGCATGAACGTCATCCTATTTTTGGAAATATAGTAGATGAAGTTGCTTATCATGAGAAATATCCAACTATCTATCATCTGCGAAAAAAATTGGTAGATTCTACTGATAAAGCGGATTTGCGCTTAATCTATTTGGCCTTAGCGCATATGATTAAGTTTCGTGGTCATTTTTTGATTGAGGGAGATTTAAATCCTGATAATAGTGATGTGGACAAACTATTTATCCAGTTGGTACAAACCTACAATCAATTATTTGAAGAAAACCCTATTAACGCAAGTGGAGTAGATGCTAAAGCGATTCTTTCTGCACGATTGAGTAAATCAAGACGATTAGAAAATCTCATTGCTCAGCTCCCCGGTGAGAAGAAAAATGGCTTATTTGGGAATCTCATTGCTTTGTCATTGGGTTTGACCCCTAATTTTAAATCAAATTTTGATTTGGCAGAAGATGCTAAATTACAGCTTTCAAAAGATACTTACGATGATGATTTAGATAATTTATTGGCGCAAATTGGAGATCAATATGCTGATTTGTTTTTGGCAGCTAAGAATTTATCAGATGCTATTTTACTTTCAGATATCCTAAGAGTAAATACTGAAATAACTAAGGCTCCCCTATCAGCTTCAATGATTAAACGCTACGATGAACATCATCAAGACTTGACTCTTTTAAAAGCTTTAGTTCGACAACAACTTCCAGAAAAGTATAAAGAAATCTTTTTTGATCAATCAAAAAACGGATATGCAGGTTATATTGATGGGGGAGCTAGCCAAGAAGAATTTTATAAATTTATCAAACCAATTTTAGAAAAAATGGATGGTACTGAGGAATTATTGGTGAAACTAAATCGTGAAGATTTGCTGCGCAAGCAACGGACCTTTGACAACGGCTCTATTCCCCATCAAATTCACTTGGGTGAGCTGCATGCTATTTTGAGAAGACAAGAAGACTTTTATCCATTTTTAAAAGACAATCGTGAGAAGATTGAAAAAATCTTGACTTTTCGAATTCCTTATTATGTTGGTCCATTGGCGCGTGGCAATAGTCGTTTTGCATGGATGACTCGGAAGTCTGAAGAAACAATTACCCCATGGAATTTTGAAGAAGTTGTCGATAAAGGTGCTTCAGCTCAATCATTTATTGAACGCATGACAAACTTTGATAAAAATCTTCCAAATGAAAAAGTACTACCAAAACATAGTTTGCTTTATGAGTATTTTACGGTTTATAACGAATTGACAAAGGTCAAATATGTTACTGAAGGAATGCGAAAACCAGCATTTCTTTCAGGTGAACAGAAGAAAGCCATTGTTGATTTACTCTTCAAAACAAATCGAAAAGTAACCGTTAAGCAATTAAAAGAAGATTATTTCAAAAAAATAGAATGTTTTGATAGTGTTGAAATTTCAGGAGTTGAAGATAGATTTAATGCTTCATTAGGTACCTACCATGATTTGCTAAAAATTATTAAAGATAAAGATTTTTTGGATAATGAAGAAAATGAAGATATCTTAGAGGATATTGTTTTAACATTGACCTTATTTGAAGATAGGGAGATGATTGAGGAAAGACTTAAAACATATGCTCACCTCTTTGATGATAAGGTGATGAAACAGCTTAAACGTCGCCGTTATACTGGTTGGGGACGTTTGTCTCGAAAATTGATTAATGGTATTAGGGATAAGCAATCTGGCAAAACAATATTAGATTTTTTGAAATCAGATGGTTTTGCCAATCGCAATTTTATGCAGCTGATCCATGATGATAGTTTGACATTTAAAGAAGACATTCAAAAAGCACAAGTGTCTGGACAAGGCGATAGTTTACATGAACATATTGCAAATTTAGCTGGTAGCCCTGCTATTAAAAAAGGTATTTTACAGACTGTAAAAGTTGTTGATGAATTGGTCAAAGTAATGGGGCGGCATAAGCCAGAAAATATCGTTATTGAAATGGCACGTGAAAATCAGACAACTCAAAAGGGCCAGAAAAATTCGCGAGAGCGTATGAAACGAATCGAAGAAGGTATCAAAGAATTAGGAAGTCAGATTCTTAAAGAGCATCCTGTTGAAAATACTCAATTGCAAAATGAAAAGCTCTATCTCTATTATCTCCAAAATGGAAGAGACATGTATGTGGACCAAGAATTAGATATTAATCGTTTAAGTGATTATGATGTCGATGCCATTGTTCCACAAAGTTTCCTTAAAGACGATTCAATAGACAATAAGGTCTTAACGCGTTCTGATAAAAATCGTGGTAAATCGGATAACGTTCCAAGTGAAGAAGTAGTCAAAAAGATGAAAAACTATTGGAGACAACTTCTAAACGCCAAGTTAATCACTCAACGTAAGTTTGATAATTTAACGAAAGCTGAACGTGGAGGTTTGAGTGAACTTGATAAAGCTGGTTTTATCAAACGCCAATTGGTTGAAACTCGCCAAATCACTAAGCATGTGGCACAAATTTTGGATAGTCGCATGAATACTAAATACGATGAAAATGATAAACTTATTCGAGAGGTTAAAGTGATTACCTTAAAATCTAAATTAGTTTCTGACTTCCGAAAAGATTTCCAATTCTATAAAGTACGTGAGATTAACAATTACCATCATGCCCATGATGCGTATCTAAATGCCGTCGTTGGAACTGCTTTGATTAAGAAATATCCAAAACTTGAATCGGAGTTTGTCTATGGTGATTATAAAGTTTATGATGTTCGTAAAATGATTGCTAAGTCTGAGCAAGAAATAGGCAAAGCAACCGCAAAATATTTCTTTTACTCTAATATCATGAACTTCTTCAAAACAGAAATTACACTTGCAAATGGAGAGATTCGCAAACGCCCTCTAATCGAAACTAATGGGGAAACTGGAGAAATTGTCTGGGATAAAGGGCGAGATTTTGCCACAGTGCGCAAAGTATTGTCCATGCCCCAAGTCAATATTGTCAAGAAAACAGAAGTACAGACAGGCGGATTCTCCAAGGAGTCAATTTTACCAAAAAGAAATTCGGACAAGCTTATTGCTCGTAAAAAAGACTGGGATCCAAAAAAATATGGTGGTTTTGATAGTCCAACGGTAGCTTATTCAGTCCTAGTGGTTGCTAAGGTGGAAAAAGGGAAATCGAAGAAGTTAAAATCCGTTAAAGAGTTACTAGGGATCACAATTATGGAAAGAAGTTCCTTTGAAAAAAATCCGATTGACTTTTTAGAAGCTAAAGGATATAAGGAAGTTAAAAAAGACTTAATCATTAAACTACCTAAATATAGTCTTTTTGAGTTAGAAAACGGTCGTAAACGGATGCTGGCTAGTGCCGGAGAATTACAAAAAGGAAATGAGCTGGCTCTGCCAAGCAAATATGTGAATTTTTTATATTTAGCTAGTCATTATGAAAAGTTGAAGGGTAGTCCAGAAGATAACGAACAAAAACAATTGTTTGTGGAGCAGCATAAGCATTATTTAGATGAGATTATTGAGCAAATCAGTGAATTTTCTAAGCGTGTTATTTTAGCAGATGCCAATTTAGATAAAGTTCTTAGTGCATATAACAAACATAGAGACAAACCAATACGTGAACAAGCAGAAAATATTATTCATTTATTTACGTTGACGAATCTTGGAGCTCCCGCTGCTTTTAAATATTTTGATACAACAATTGATCGTAAACGATATACGTCTACAAAAGAAGTTTTAGATGCCACTCTTATCCATCAATCCATCACTGGTCTTTATGAAACACGCATTGATTTGAGTCAGCTAGGAGGTGACTAAGTCGACCTCGAGACTAGTCAAGGTCGGCAATTCTGCAGTACTAGGACGCCGCCAAGCCAGCTTAAACCCAGCTCAATGAGCTGGGTTTTTTGTTTGTTAAAAATGAAGAAGAAACTGTGAAGCGTATTTATAGCAAAGCACTCAAAAGTTTACCTTATGGGTGCTTTTTTCGTGCTTTTTTGAAAAGACAAAAAAAAGAACCTTGCCAAGCAAGATTCTTTTGATAGCGCTATCGCTGAGCGCCGGTCGCTACCATTACCAGTTGGTCTGGTGTCAAAAATAATAATAACCGGGCAGGCCATGTCTGCCCGTATTTCGCGTAAGGAAATCCATTATGTACTATTTCTGGTGATGAAATCAACGTAACATTTAAAGCTGTCAAAGCCAAAGTCATGAGATGGCGTATGGAGCGTAAAGCTGACAAGAGCGGTGTTGCGATGATTGAGATGACCTTCCTTGCACCAAGTGAATTGCCTCAAGAAAGCACTCAATCAAAGATTCTTGTAGATGGAAAAGAACTTGCTGATTTCGCTGAAAATCGTCAAGACTATCAAATTACCTATAAAGGTCAACGGCCAAAAGTCTCAGTTGAAGAAAACAATCAAGTAGCTTCAACTGTGGTAGATAGTGGAGAAGATAGCCTTCCAGTACTTGTTCGCCTCGTTTCAGAAAGTGGAAAACAAGTCAAGGAATACCGTATCCAGTTGACTAAGGAAAAACCAGTTTCTGCTGTACAAGAAGATCTTCCAAAACTCGAATTTGTTGAAAAAGATTTGGCCTACAAGACAGTTGAGAAAAAAGATTCAACACTGTATCTAGGTGAAACTCGTGTAGAACAAGAAGGAAAAGTTGGAAAAGAACGTATCTTTACAGTGATTAATCCTGATGGAAGTAAGGAAGAAAAACTCCGTGAAGTGGTAGAAGTTCCGACAGACCGCATCGTCTTGGTTGGAACCAAACCAGTAGCTCAAGAAGCTAAAAAACCACAAGTGTCAGAAAAAGCAGATACAAAACCAATTGATTCAAGTGAAGCTGATCAAACTAATAAAGCCCAGTTACCAAATACAGGTAGTGCGGCAAGCCAAGCAGCAGTAGCAGCAGGTTTAGCCTGCCTCGCGCGTTTCGGTGATGACGGTGAAAACCTCTGACACATGCAGCTCCCGGAGACGGTCACAGCTTGTCTGTAAGCGGATGCCGGGAGCAGACAAGCCCGTCAGGGCGCGTCAGCGGGTGTTGGCGGGTGTCGGGGCGCAGCCATGACCCAGTCACGTAGCGATAGCGGAGTGTATACTGGCTTAACTATGCGGCATCAGAGCAGATTGTACTGAGAGTGCACCATATGCGGTGTGAAATACCGCACAGATGCGTAAGGAGAAAATACCGCATCAGGCGCTCTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACTCAAAGGCGGTAA >pV1-PsspA (SEQ ID No: 228)GAGCCTATGGAAAAACGCTTTGCCCCACACAGGCTCTTGAACAAGGGATAACAATTTGTCATAGCTGTATTCGTTACAAGGAGGATTTTCGAAAAAACACCCTAACGGGTGTTTTTTTATAGCTGGTCTCCCCAAGTGCTGTAAAAAACGCCGAATGAAGCGGATGAAATTGCTCATCGTCTCGTGAAAAAGCCGAAGAAGGTTAAGCCTGGGTATAAAAAGAAAATGAGCTATGAGATGGAGAAAGCCATAACCATGAGTGATAACACTGGTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTTTTTTTCTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCCTCAATGATCTCCTTATCCGGTTAAGATGGCAAGCTTGACAAGTATTTCTTCAGAATTTACAATGAAGTTTACATGACGCTCTTAAAGGGGGTTTTAGATACCAGAGATGGATAAGAAATACTCAATAGGCTTAGATATCGGCACAAATAGCGTCGGATGGGCGGTGAAACACGCATTGATTTGAGTCAGCTAGGAGGTGACTGATAATCAAATGTCAGACGAAAATGCCAATTATTGAAGCGGCTAACGCCGCTTTTTTTGTTTCTGGTCTCCCTTGCTTGTACTTTACAGTATAGCTTCTAGAGATCTGCAGTGACTGGAGCTTCTAGAGATCTGCAGTGACTGGGAAAACCCTGGCGACTAGTCTTGGACTCCTGTTGATAGATCCAGTAATGACCTCAGAACTCCATCTGGATTTGTTCAGAACGCTCGGTTGCCGCCGGGCGTTTTTTATTGGTGAGAATCCAGGGGTCCCCAATAATTACGATTTAAATCCTTCAAACTTCCCAAAGGCGAGCCCTAGTGACATTAGAAAACCGACTGTAAAAAGTACAGTCGGCATTATCTCATATTATAAAAGCCAGTCATTAGGCCTATCTGACAATTCCTGAATAGAGTTCATAAACAATCCTGCATGATAACCATCACAAACAGAATGATGTACCTGTAAAGATAGCGGTAAATATATTGAATTACCTTTATTAATGAATTTTCCTGCTGTAATAATGGGTAGAAGGTAATTACTATTATTATTGATATTTAAGTTAAACCCAGTAAATGAAGTCCATGGAATAATAGAAAGAGAAAAAGCATTTTCAGGTATAGGTGTTTTGGGAAACAATTTCCCCGAACCATTATATTTCTCTACATCAGAAAGGTATAAATCATAAAACTCTTTGAAGTCATTCTTTACAGGAGTCCAAATACCAGAGAATGTTTTAGATACACCATCAAAAATTGTATAAAGTGGCTCTAACTTATCCCAATAACCTAACTCTCCGTCGCTATTGTAACCAGTTCTAAAAGCTGTATTTGAGTTTATCACCCTTGTCACTAAGAAAATAAATGCAGGGTAAAATTTATATCCTTCTTGTTTTATGTTTCGGTATAAAACACTAATATCAATTTCTGTGGTTATACTAAAAGTCGTTTGTTGGTTCAAATAATGATTAAATATCTCTTTTCTCTTCCAATTGTCTAAATCAATTTTATTAAAGTTCATTTGATATGCCTCCTAAATTTTTATCTAAAGTGAATTTAGGAGGCTTACTTGTCTGCTTTCTTCATTAGAATCAATCCTTTTTTAAAAGTCAATCCCGTTTGTTGAAGACTTTTGTCCTTTTCCGCTGCATAAACAATATGGCCCGTTTGTTGAACTACTCTTTAATAAAATAATTTTTCCGTTCCCAATTCCACATTGCAATAATAGAAAATCCATCTTCATCGGCTTTTTCGTCATCATCTGTATGAATCAAATCGCCTTCTTCTGTGTCATCAAGGTTTAATTTTTTATGTATTTCTTTTAACAAACCACCATAGGAGATTAACCTTTTACGGTGTAAACCTTCCTCCAAATCAGACAAACGTTTCAAATTCTTTTCTTCATCATCGGTCATAAAATCCGTATCCTTTACAGGATATTTTGCAGTTTCGTCAATTGCCGATTGTATATCCGATTTATATTTATTTTTCGGTCGAATCATTTGAACTTTTACATTTGGATCATAGTCTAATTTCATTGCCTTTTTCCAAAATTGAATCCATTGTTTTTGATTCACGTAGTTTTCTGTATTCTTAAAATAAGTTGGTTCCACACATACCAATACATGCATGTGCTGATTATAAGAATTATCTTTATTATTTATTGTCACTTCCGTTGCACGCATAAAACCAACAAGATTTTTATTAATTTTTTTATATTGCATCATTCGGCGAAATCCTTGAGCCATATCTGACAAACTCTTATTTAATTCTTCGCCATCATAAACATTTTTAACTGTTAATGTGAGAAACAACCAACGAACTGTTGGCTTTTGTTTAATAACTTCAGCAACAACCTTTTGTGACTGAATGCCATGTTTCATTGCTCTCCTCCAGTTGCACATTGGACAAAGCCTGGATTTACAAAACCACACTCGATACAACTTTCTTTCGCCTGTTTCACGATTTTGTTTATACTCTAATATTTCAGCACAATCTTTTACTCTTTCAGCCTTTTTAAATTCAAGAATATGCAGAAGTTCAAAGTAATCAACATTAGCGATTTTCTTTTCTCTCCATGGTCTCACTTTTCCACTTTTTGTCTTGTCCACTAAAACCCTTGATTTTTCATCTGAATAAATGCTACTATTAGGACACATAATATTAAAAGAAACCCCCATCTATTTAGTTATTTGTTTGGTCACTTATAACTTTAACAGATGGGGTTTTTCTGTGCAACCAATTTTAAGGGTTTTCCAATACTTTAAAACACATACATACCAACACTTCAACGCACCTTTCAGCAACTAAAATAAAAATGACGTTATTTCTATATGTATCAAGATAAGAAAGAACAAGTTCAAAACCATCAAAAAAAGACACCTTTTCAGGTGCTTTTTTTATTTTATAAACTCATTCCCTGATCTCGACTTCGTTCTTTTTTTACCTCTCGGTTATGAGTTAGTTCAAATTCGTTCTTTTTAGGTTCTAAATCGTGTTTTTCTTGGAATTGTGCTGTTTTATCCTTTACCTTGTCTACAAACCCCTTAAAAACGTTTTTAAAGGCTTTTAAGCGTCTGTACGTTCCTTAAGGAATTATTCCTTAGTGCTTTCTAGGTTAATGTCATGATAATAATGGTTTCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTCCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTGTTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGCAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCTTAATAAGATGATCTTCTTGAGATCGTTTTGGTCTGCGCGTAATCTCTTGCTCTGAAAACGAAAAAACCGCCTTGCAGGGAGGTTTTTCGAAGGTTCTCTGAGCTACCAACTCTTTGAACCGAGGTAACTGGCTTGCAGGAGCGCAGTCACCAAAACTTGTCCTTTCAGTTTAGCCTTAACCGGCGCATGACTTCAAGACTAACTCCTCTAAATCAATTACCAGTGGCTGCTGCCAGTGGTGCTTTTGCATGTCTTTCCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGACTGAACGGGGGGTTCGTGCATACAGTCCAGCTTGGAGCGAACTGCCTACCCGGAACTGAGTGTCAGGCGTGGAATGAGACAAACGCGGCCATAACAGCGGAATGACACCGGTAAACCGAAAGGCAGGAACAGGAGAGCGCACGAGGGAGCCGCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCACTGATTTGAGCGTCAGATTTCGTGATGCTTGTCAGGGGGCGGAGCCTATGGAAAAACGCTTTGCCC >pCas9g1-cons(SEQ ID No: 229) aataggcttagatatcggcacaaatagcgtcggatgggCGGTGATCACTGATGAATATAAGGTTCCGTCTAAAAAGTTCAAGGTTCTGGGAAATACAGACCGCCACAGTATCAAAAAAAATCTTATAGGGGCTCTTTTATTTGACAGTGGAGAGACAGCGGAAGCGACTCGTCTCAAACGGACAGCTCGTAGAAGGTATACACGTCGGAAGAATCGTATTTGTTATCTACAGGAGATTTTTTCAAATGAGATGGCGAAAGTAGATGATAGTTTCTTTCATCGACTTGAAGAGTCTTTTTTGGTGGAAGAAGACAAGAAGCATGAACGTCATCCTATTTTTGGAAATATAGTAGATGAAGTTGCTTATCATGAGAAATATCCAACTATCTATCATCTGCGAAAAAAATTGGTAGATTCTACTGATAAAGCGGATTTGCGCTTAATCTATTTGGCCTTAGCGCATATGATTAAGTTTCGTGGTCATTTTTTGATTGAGGGAGATTTAAATCCTGATAATAGTGATGTGGACAAACTATTTATCCAGTTGGTACAAACCTACAATCAATTATTTGAAGAAAACCCTATTAACGCAAGTGGAGTAGATGCTAAAGCGATTCTTTCTGCACGATTGAGTAAATCAAGACGATTAGAAAATCTCATTGCTCAGCTCCCCGGTGAGAAGAAAAATGGCTTATTTGGGAATCTCATTGCTTTGTCATTGGGTTTGACCCCTAATTTTAAATCAAATTTTGATTTGGCAGAAGATGCTAAATTACAGCTTTCAAAAGATACTTACGATGATGATTTAGATAATTTATTGGCGCAAATTGGAGATCAATATGCTGATTTGTTTTTGGCAGCTAAGAATTTATCAGATGCTATTTTACTTTCAGATATCCTAAGAGTAAATACTGAAATAACTAAGGCTCCCCTATCAGCTTCAATGATTAAACGCTACGATGAACATCATCAAGACTTGACTCTTTTAAAAGCTTTAGTTCGACAACAACTTCCAGAAAAGTATAAAGAAATCTTTTTTGATCAATCAAAAAACGGATATGCAGGTTATATTGATGGGGGAGCTAGCCAAGAAGAATTTTATAAATTTATCAAACCAATTTTAGAAAAAATGGATGGTACTGAGGAATTATTGGTGAAACTAAATCGTGAAGATTTGCTGCGCAAGCAACGGACCTTTGACAACGGCTCTATTCCCCATCAAATTCACTTGGGTGAGCTGCATGCTATTTTGAGAAGACAAGAAGACTTTTATCCATTTTTAAAAGACAATCGTGAGAAGATTGAAAAAATCTTGACTTTTCGAATTCCTTATTATGTTGGTCCATTGGCGCGTGGCAATAGTCGTTTTGCATGGATGACTCGGAAGTCTGAAGAAACAATTACCCCATGGAATTTTGAAGAAGTTGTCGATAAAGGTGCTTCAGCTCAATCATTTATTGAACGCATGACAAACTTTGATAAAAATCTTCCAAATGAAAAAGTACTACCAAAACATAGTTTGCTTTATGAGTATTTTACGGTTTATAACGAATTGACAAAGGTCAAATATGTTACTGAAGGAATGCGAAAACCAGCATTTCTTTCAGGTGAACAGAAGAAAGCCATTGTTGATTTACTCTTCAAAACAAATCGAAAAGTAACCGTTAAGCAATTAAAAGAAGATTATTTCAAAAAAATAGAATGTTTTGATAGTGTTGAAATTTCAGGAGTTGAAGATAGATTTAATGCTTCATTAGGTACCTACCATGATTTGCTAAAAATTATTAAAGATAAAGATTTTTTGGATAATGAAGAAAATGAAGATATCTTAGAGGATATTGTTTTAACATTGACCTTATTTGAAGATAGGGAGATGATTGAGGAAAGACTTAAAACATATGCTCACCTCTTTGATGATAAGGTGATGAAACAGCTTAAACGTCGCCGTTATACTGGTTGGGGACGTTTGTCTCGAAAATTGATTAATGGTATTAGGGATAAGCAATCTGGCAAAACAATATTAGATTTTTTGAAATCAGATGGTTTTGCCAATCGCAATTTTATGCAGCTGATCCATGATGATAGTTTGACATTTAAAGAAGACATTCAAAAAGCACAAGTGTCTGGACAAGGCGATAGTTTACATGAACATATTGCAAATTTAGCTGGTAGCCCTGCTATTAAAAAAGGTATTTTACAGACTGTAAAAGTTGTTGATGAATTGGTCAAAGTAATGGGGCGGCATAAGCCAGAAAATATCGTTATTGAAATGGCACGTGAAAATCAGACAACTCAAAAGGGCCAGAAAAATTCGCGAGAGCGTATGAAACGAATCGAAGAAGGTATCAAAGAATTAGGAAGTCAGATTCTTAAAGAGCATCCTGTTGAAAATACTCAATTGCAAAATGAAAAGCTCTATCTCTATTATCTCCAAAATGGAAGAGACATGTATGTGGACCAAGAATTAGATATTAATCGTTTAAGTGATTATGATGTCGATCACATTGTTCCACAAAGTTTCCTTAAAGACGATTCAATAGACAATAAGGTCTTAACGCGTTCTGATAAAAATCGTGGTAAATCGGATAACGTTCCAAGTGAAGAAGTAGTCAAAAAGATGAAAAACTATTGGAGACAACTTCTAAACGCCAAGTTAATCACTCAACGTAAGTTTGATAATTTAACGAAAGCTGAACGTGGAGGTTTGAGTGAACTTGATAAAGCTGGTTTTATCAAACGCCAATTGGTTGAAACTCGCCAAATCACTAAGCATGTGGCACAAATTTTGGATAGTCGCATGAATACTAAATACGATGAAAATGATAAACTTATTCGAGAGGTTAAAGTGATTACCTTAAAATCTAAATTAGTTTCTGACTTCCGAAAAGATTTCCAATTCTATAAAGTACGTGAGATTAACAATTACCATCATGCCCATGATGCGTATCTAAATGCCGTCGTTGGAACTGCTTTGATTAAGAAATATCCAAAACTTGAATCGGAGTTTGTCTATGGTGATTATAAAGTTTATGATGTTCGTAAAATGATTGCTAAGTCTGAGCAAGAAATAGGCAAAGCAACCGCAAAATATTTCTTTTACTCTAATATCATGAACTTCTTCAAAACAGAAATTACACTTGCAAATGGAGAGATTCGCAAACGCCCTCTAATCGAAACTAATGGGGAAACTGGAGAAATTGTCTGGGATAAAGGGCGAGATTTTGCCACAGTGCGCAAAGTATTGTCCATGCCCCAAGTCAATATTGTCAAGAAAACAGAAGTACAGACAGGCGGATTCTCCAAGGAGTCAATTTTACCAAAAAGAAATTCGGACAAGCTTATTGCTCGTAAAAAAGACTGGGATCCAAAAAAATATGGTGGTTTTGATAGTCCAACGGTAGCTTATTCAGTCCTAGTGGTTGCTAAGGTGGAAAAAGGGAAATCGAAGAAGTTAAAATCCGTTAAAGAGTTACTAGGGATCACAATTATGGAAAGAAGTTCCTTTGAAAAAAATCCGATTGACTTTTTAGAAGCTAAAGGATATAAGGAAGTTAAAAAAGACTTAATCATTAAACTACCTAAATATAGTCTTTTTGAGTTAGAAAACGGTCGTAAACGGATGCTGGCTAGTGCCGGAGAATTACAAAAAGGAAATGAGCTGGCTCTGCCAAGCAAATATGTGAATTTTTTATATTTAGCTAGTCATTATGAAAAGTTGAAGGGTAGTCCAGAAGATAACGAACAAAAACAATTGTTTGTGGAGCAGCATAAGCATTATTTAGATGAGATTATTGAGCAAATCAGTGAATTTTCTAAGCGTGTTATTTTAGCAGATGCCAATTTAGATAAAGTTCTTAGTGCATATAACAAACATAGAGACAAACCAATACGTGAACAAGCAGAAAATATTATTCATTTATTTACGTTGACGAATCTTGGAGCTCCCGCTGCTTTTAAATATTTTGATACAACAATTGATCGTAAACGATATACGTCTACAAAAGAAGTTTTAGATGCCACTCTTATCCATCAATCCATCACTGGTCTTTATgaaacacgcattgatttgagtcagctaggaggtgactgaTAATCAAATGTCAGACGAAAATGCCAATTATTGAAGCGGCTAACGCCGCTTTTTTTGTTTCTGGTCTCCCTTGCTTGTACTTTACAGTATAGCTTCTAGAGATCTGCAGTGACTGGAGCTTCTAGAGATCTGCAGTGACTGGGAAAACCCTGGCGACTAGTCTTGGACTCCTGTTGATAGATCCAGTAATGACCTCAGAACTCCATCTGGATTTGTTCAGAACGCTCGGTTGCCGCCGGGCGTTTTTTATTGGTGAGAATCCAGGGGTCCCCAATAATTACGATTTAAATCCTTCAAACTTCCCAAAGGCGAGCCCTAGTGACATTAGAAAACCGACTGTAAAAAGTACAGTCGGCATTATCTCATATTATAAAAGCCAGTCATTAGGCCTATCTGACAATTCCTGAATAGAGTTCATAAACAATCCTGCATGATAACCATCACAAACAGAATGATGTACCTGTAAAGATAGCGGTAAATATATTGAATTACCTTTATTAATGAATTTTCCTGCTGTAATAATGGGTAGAAGGTAATTACTATTATTATTGATATTTAAGTTAAACCCAGTAAATGAAGTCCATGGAATAATAGAAAGAGAAAAAGCATTTTCAGGTATAGGTGTTTTGGGAAACAATTTCCCCGAACCATTATATTTCTCTACATCAGAAAGGTATAAATCATAAAACTCTTTGAAGTCATTCTTTACAGGAGTCCAAATACCAGAGAATGTTTTAGATACACCATCAAAAATTGTATAAAGTGGCTCTAACTTATCCCAATAACCTAACTCTCCGTCGCTATTGTAACCAGTTCTAAAAGCTGTATTTGAGTTTATCACCCTTGTCACTAAGAAAATAAATGCAGGGTAAAATTTATATCCTTCTTGTTTTATGTTTCGGTATAAAACACTAATATCAATTTCTGTGGTTATACTAAAAGTCGTTTGTTGGTTCAAATAATGATTAAATATCTCTTTTCTCTTCCAATTGTCTAAATCAATTTTATTAAAGTTCATTTGATATGCCTCCTAAATTTTTATCTAAAGTGAATTTAGGAGGCTTACTTGTCTGCTTTCTTCATTAGAATCAATCCTTTTTTAAAAGTCAATCCCGTTTGTTGAAGACTTTTGTCCTTTTCCGCTGCATAAACAATATGGCCCGTTTGTTGAACTACTCTTTAATAAAATAATTTTTCCGTTCCCAATTCCACATTGCAATAATAGAAAATCCATCTTCATCGGCTTTTTCGTCATCATCTGTATGAATCAAATCGCCTTCTTCTGTGTCATCAAGGTTTAATTTTTTATGTATTTCTTTTAACAAACCACCATAGGAGATTAACCTTTTACGGTGTAAACCTTCCTCCAAATCAGACAAACGTTTCAAATTCTTTTCTTCATCATCGGTCATAAAATCCGTATCCTTTACAGGATATTTTGCAGTTTCGTCAATTGCCGATTGTATATCCGATTTATATTTATTTTTCGGTCGAATCATTTGAACTTTTACATTTGGATCATAGTCTAATTTCATTGCCTTTTTCCAAAATTGAATCCATTGTTTTTGATTCACGTAGTTTTCTGTATTCTTAAAATAAGTTGGTTCCACACATACCAATACATGCATGTGCTGATTATAAGAATTATCTTTATTATTTATTGTCACTTCCGTTGCACGCATAAAACCAACAAGATTTTTATTAATTTTTTTATATTGCATCATTCGGCGAAATCCTTGAGCCATATCTGACAAACTCTTATTTAATTCTTCGCCATCATAAACATTTTTAACTGTTAATGTGAGAAACAACCAACGAACTGTTGGCTTTTGTTTAATAACTTCAGCAACAACCTTTTGTGACTGAATGCCATGTTTCATTGCTCTCCTCCAGTTGCACATTGGACAAAGCCTGGATTTACAAAACCACACTCGATACAACTTTCTTTCGCCTGTTTCACGATTTTGTTTATACTCTAATATTTCAGCACAATCTTTTACTCTTTCAGCCTTTTTAAATTCAAGAATATGCAGAAGTTCAAAGTAATCAACATTAGCGATTTTCTTTTCTCTCCATGGTCTCACTTTTCCACTTTTTGTCTTGTCCACTAAAACCCTTGATTTTTCATCTGAATAAATGCTACTATTAGGACACATAATATTAAAAGAAACCCCCATCTATTTAGTTATTTGTTTGGTCACTTATAACTTTAACAGATGGGGTTTTTCTGTGCAACCAATTTTAAGGGTTTTCCAATACTTTAAAACACATACATACCAACACTTCAACGCACCTTTCAGCAACTAAAATAAAAATGACGTTATTTCTATATGTATCAAGATAAGAAAGAACAAGTTCAAAACCATCAAAAAAAGACACCTTTTCAGGTGCTTTTTTTATTTTATAAACTCATTCCCTGATCTCGACTTCGTTCTTTTTTTACCTCTCGGTTATGAGTTAGTTCAAATTCGTTCTTTTTAGGTTCTAAATCGTGTTTTTCTTGGAATTGTGCTGTTTTATCCTTTACCTTGTCTACAAACCCCTTAAAAACGTTTTTAAAGGCTTTTAAGCGTCTGTACGTTCCTTAAGGAATTATTCCTTAGTGCTTTCTAGGTTAATGTCATGATAATAATGGTTTCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTCCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTGTTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGCAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCTTAATAAGATGATCTTCTTGAGATCGTTTTGGTCTGCGCGTAATCTCTTGCTCTGAAAACGAAAAAACCGCCTTGCAGGGAGGTTTTTCGAAGGTTCTCTGAGCTACCAACTCTTTGAACCGAGGTAACTGGCTTGCAGGAGCGCAGTCACCAAAACTTGTCCTTTCAGTTTAGCCTTAACCGGCGCATGACTTCAAGACTAACTCCTCTAAATCAATTACCAGTGGCTGCTGCCAGTGGTGCTTTTGCATGTCTTTCCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGACTGAACGGGGGGTTCGTGCATACAGTCCAGCTTGGAGCGAACTGCCTACCCGGAACTGAGTGTCAGGCGTGGAATGAGACAAACGCGGCCATAACAGCGGAATGACACCGGTAAACCGAAAGGCAGGAACAGGAGAGCGCACGAGGGAGCCGCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCACTGATTTGAGCGTCAGATTTCGTGATGCTTGTCAGGGGGCGGAGCCTATGGAAAAACGCTTTGCCCGAGCCTATGGAAAAACGCTTTGCCCCACACAGGCTCTTGAACAAGGGATAACAATTTGTCATAGCTGTATTCGTTACAAGGAGGATTTTCGAAAAAACACCCTAACGGGTGTTTTTTTATAGCTGGTCTCCCCAAGTGCTGTAAAAAACGCCGAATGAAGCGGATGAAATTGCTCATCGTCTCGTGAAAAAGCCGAAGAAGGTTAAGCCTGGGTATAAAAAGAAAATGAGCTATGAGATGGAGAAAGCCATAACCATGAGTGATAACACTGGTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTTTTTTTCTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCCTCAATGATCTCCTTATCCGGTTAAGATGGCAAGCTTGACAAGTATTTCTTCAGAATTTACAATGAAGTTTACATGACGCTCTTAAAGGGGGTTTTAGATACCAGAGATGGATAAGAAATACTC >pCas9g2-cons(SEQ ID No: 230)AGGTCAGACGCGATTTCCTGGGTGCTCGAGCCATGGGAAAGCGGTGGTGGAAAAAACGCCGAATGAAGCGGATGAAATTGCTCATCGTCTCGTGAAAAAGCCGAAGAAGGTTAAGCCTGGGTATAAAAAGAAAATGAGCTATGAGATGGAGAAATTGAAGTCATGCGCCGGTTAGTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTTTTTTTCTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCCTCAATGATCCGACAGGAAGTGGTATTAGCGACTCCTACAAGGAATAGGTGTCTGGGTCATGCAGTGACTGGGAAAACCCTGGCGACTAGTCTTGGACTCCTGTTGATAGATCCAGTAATGACCTCAGAACTCCATCTGGATTTGTTCAGAACGCTCGGTTGCCGCCGGGCGTTTTTTATTGGTGAGAATCCAGGGGTCCCCAATAATTACGATTTAAATCCTTCAAACTTCCCAAAGGCGAGCCCTAGTGACATTAGAAAACCGACTGTAAAAAGTACAGTCGGCATTATCTCATATTATAAAAGCCAGTCATTAGGCCTATCTGACAATTCCTGAATAGAGTTCATAAACAATCCTGCATGATAACCATCACAAACAGAATGATGTACCTGTAAAGATAGCGGTAAATATATTGAATTACCTTTATTAATGAATTTTCCTGCTGTAATAATGGGTAGAAGGTAATTACTATTATTATTGATATTTAAGTTAAACCCAGTAAATGAAGTCCATGGAATAATAGAAAGAGAAAAAGCATTTTCAGGTATAGGTGTTTTGGGAAACAATTTCCCCGAACCATTATATTTCTCTACATCAGAAAGGTATAAATCATAAAACTCTTTGAAGTCATTCTTTACAGGAGTCCAAATACCAGAGAATGTTTTAGATACACCATCAAAAATTGTATAAAGTGGCTCTAACTTATCCCAATAACCTAACTCTCCGTCGCTATTGTAACCAGTTCTAAAAGCTGTATTTGAGTTTATCACCCTTGTCACTAAGAAAATAAATGCAGGGTAAAATTTATATCCTTCTTGTTTTATGTTTCGGTATAAAACACTAATATCAATTTCTGTGGTTATACTAAAAGTCGTTTGTTGGTTCAAATAATGATTAAATATCTCTTTTCTCTTCCAATTGTCTAAATCAATTTTATTAAAGTTCATTTGATATGCCTCCTAAATTTTTATCTAAAGTGAATTTAGGAGGCTTACTTGTCTGCTTTCTTCATTAGAATCAATCCTTTTTTAAAAGTCAATCCCGTTTGTTGAAGACTTTTGTCCTTTTCCGCTGCATAAACAATATGGCCCGTTTGTTGAACTACTCTTTAATAAAATAATTTTTCCGTTCCCAATTCCACATTGCAATAATAGAAAATCCATCTTCATCGGCTTTTTCGTCATCATCTGTATGAATCAAATCGCCTTCTTCTGTGTCATCAAGGTTTAATTTTTTATGTATTTCTTTTAACAAACCACCATAGGAGATTAACCTTTTACGGTGTAAACCTTCCTCCAAATCAGACAAACGTTTCAAATTCTTTTCTTCATCATCGGTCATAAAATCCGTATCCTTTACAGGATATTTTGCAGTTTCGTCAATTGCCGATTGTATATCCGATTTATATTTATTTTTCGGTCGAATCATTTGAACTTTTACATTTGGATCATAGTCTAATTTCATTGCCTTTTTCCAAAATTGAATCCATTGTTTTTGATTCACGTAGTTTTCTGTATTCTTAAAATAAGTTGGTTCCACACATACCAATACATGCATGTGCTGATTATAAGAATTATCTTTATTATTTATTGTCACTTCCGTTGCACGCATAAAACCAACAAGATTTTTATTAATTTTTTTATATTGCATCATTCGGCGAAATCCTTGAGCCATATCTGACAAACTCTTATTTAATTCTTCGCCATCATAAACATTTTTAACTGTTAATGTGAGAAACAACCAACGAACTGTTGGCTTTTGTTTAATAACTTCAGCAACAACCTTTTGTGACTGAATGCCATGTTTCATTGCTCTCCTCCAGTTGCACATTGGACAAAGCCTGGATTTACAAAACCACACTCGATACAACTTTCTTTCGCCTGTTTCACGATTTTGTTTATACTCTAATATTTCAGCACAATCTTTTACTCTTTCAGCCTTTTTAAATTCAAGAATATGCAGAAGTTCAAAGTAATCAACATTAGCGATTTTCTTTTCTCTCCATGGTCTCACTTTTCCACTTTTTGTCTTGTCCACTAAAACCCTTGATTTTTCATCTGAATAAATGCTACTATTAGGACACATAATATTAAAAGAAACCCCCATCTATTTAGTTATTTGTTTGGTCACTTATAACTTTAACAGATGGGGTTTTTCTGTGCAACCAATTTTAAGGGTTTTCCAATACTTTAAAACACATACATACCAACACTTCAACGCACCTTTCAGCAACTAAAATAAAAATGACGTTATTTCTATATGTATCAAGATAAGAAAGAACAAGTTCAAAACCATCAAAAAAAGACACCTTTTCAGGTGCTTTTTTTATTTTATAAACTCATTCCCTGATCTCGACTTCGTTCTTTTTTTACCTCTCGGTTATGAGTTAGTTCAAATTCGTTCTTTTTAGGTTCTAAATCGTGTTTTTCTTGGAATTGTGCTGTTTTATCCTTTACCTTGTCTACAAACCCCTTAAAAACGTTTTTAAAGGCTTTTAAGCGTCTGTACGTTCCTTAAGGAATTATTCCTTAGTGCTTTCTAGGTTAATGTCATGATAATAATGGTTTCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTCCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTGTTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGCAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCTTAATAAGATGATCTTCTTGAGATCGTTTTGGTCTGCGCGTAATCTCTTGCTCTGAAAACGAAAAAACCGCCTTGCAGGGAGGTTTTTCGAAGGTTCTCTGAGCTACCAACTCTTTGAACCGAGGTAACTGGCTTGCAGGAGCGCAGTCACCAAAACTTGTCCTTTCAGTTTAGCCTTAACCGGCGCATGACTTCAAGACTAACTCCTCTAAATCAATTACCAGTGGCTGCTGCCAGTGGTGCTTTTGCATGTCTTTCCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGACTGAACGGGGGGTTCGTGCATACAGTCCAGCTTGGAGCGAACTGCCTACCCGGAACTGAGTGTCAGGCGTGGAATGAGACAAACGCGGCCATAACAGCGGAATGACACCGGTAAACCGAAAGGCAGGAACAGGAGAGCGCACGAGGGAGCCGCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCACTGATTTGAGCGTCAGATTTCGTGATGCTTGTCAGGGGGCGGAGCCTATGGAAAAACGCTTTGCCCGAGCCTATGGAAAAACGCTTTGCCCCACACAGGCTCTTGAACAAGGGATAACAATTTGTCATAGCTGTATTCGTTACAAGGAGGATTTTCGAAAAAACACCCTAACGGGTGTTTTTTTATAGCTGGTCTCCCCAAGTGCTGTAAAAAACGCCGAATGAAGCGGATGAAATTGCTCATCGTCTCGTGAAAAAGCCGAAGAAGGTTAAGCCTGGGTATAAAAAGAAAATGAGCTATGAGATGGAGAAAGCCATAACCATGAGTGATAACACTGGTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTTTTTTTCTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCCTCAATGATCTCCTTATCCGGTTAAGATGGCAAGCTTGACAAGTATTTCTTCAGAATTTACAATGAAGTTTACATGACGCTCTTAAAGGGGGTTTTAGATACCAGAGATGGATAAGAAATACTCAATAGGCTTAGATATCGGCACAAATAGCGTCGGATGGGCGGTGATCACTGATGAATATAAGGTTCCGTCTAAAAAGTTCAAGGTTCTGGGAAATACAGACCGCCACAGTATCAAAAAAAATCTTATAGGGGCTCTTTTATTTGACAGTGGAGAGACAGCGGAAGCGACTCGTCTCAAACGGACAGCTCGTAGAAGGTATACACGTCGGAAGAATCGTATTTGTTATCTACAGGAGATTTTTTCAAATGAGATGGCGAAAGTAGATGATAGTTTCTTTCATCGACTTGAAGAGTCTTTTTTGGTGGAAGAAGACAAGAAGCATGAACGTCATCCTATTTTTGGAAATATAGTAGATGAAGTTGCTTATCATGAGAAATATCCAACTATCTATCATCTGCGAAAAAAATTGGTAGATTCTACTGATAAAGCGGATTTGCGCTTAATCTATTTGGCCTTAGCGCATATGATTAAGTTTCGTGGTCATTTTTTGATTGAGGGAGATTTAAATCCTGATAATAGTGATGTGGACAAACTATTTATCCAGTTGGTACAAACCTACAATCAATTATTTGAAGAAAACCCTATTAACGCAAGTGGAGTAGATGCTAAAGCGATTCTTTCTGCACGATTGAGTAAATCAAGACGATTAGAAAATCTCATTGCTCAGCTCCCCGGTGAGAAGAAAAATGGCTTATTTGGGAATCTCATTGCTTTGTCATTGGGTTTGACCCCTAATTTTAAATCAAATTTTGATTTGGCAGAAGATGCTAAATTACAGCTTTCAAAAGATACTTACGATGATGATTTAGATAATTTATTGGCGCAAATTGGAGATCAATATGCTGATTTGTTTTTGGCAGCTAAGAATTTATCAGATGCTATTTTACTTTCAGATATCCTAAGAGTAAATACTGAAATAACTAAGGCTCCCCTATCAGCTTCAATGATTAAACGCTACGATGAACATCATCAAGACTTGACTCTTTTAAAAGCTTTAGTTCGACAACAACTTCCAGAAAAGTATAAAGAAATCTTTTTTGATCAATCAAAAAACGGATATGCAGGTTATATTGATGGGGGAGCTAGCCAAGAAGAATTTTATAAATTTATCAAACCAATTTTAGAAAAAATGGATGGTACTGAGGAATTATTGGTGAAACTAAATCGTGAAGATTTGCTGCGCAAGCAACGGACCTTTGACAACGGCTCTATTCCCCATCAAATTCACTTGGGTGAGCTGCATGCTATTTTGAGAAGACAAGAAGACTTTTATCCATTTTTAAAAGACAATCGTGAGAAGATTGAAAAAATCTTGACTTTTCGAATTCCTTATTATGTTGGTCCATTGGCGCGTGGCAATAGTCGTTTTGCATGGATGACTCGGAAGTCTGAAGAAACAATTACCCCATGGAATTTTGAAGAAGTTGTCGATAAAGGTGCTTCAGCTCAATCATTTATTGAACGCATGACAAACTTTGATAAAAATCTTCCAAATGAAAAAGTACTACCAAAACATAGTTTGCTTTATGAGTATTTTACGGTTTATAACGAATTGACAAAGGTCAAATATGTTACTGAAGGAATGCGAAAACCAGCATTTCTTTCAGGTGAACAGAAGAAAGCCATTGTTGATTTACTCTTCAAAACAAATCGAAAAGTAACCGTTAAGCAATTAAAAGAAGATTATTTCAAAAAAATAGAATGTTTTGATAGTGTTGAAATTTCAGGAGTTGAAGATAGATTTAATGCTTCATTAGGTACCTACCATGATTTGCTAAAAATTATTAAAGATAAAGATTTTTTGGATAATGAAGAAAATGAAGATATCTTAGAGGATATTGTTTTAACATTGACCTTATTTGAAGATAGGGAGATGATTGAGGAAAGACTTAAAACATATGCTCACCTCTTTGATGATAAGGTGATGAAACAGCTTAAACGTCGCCGTTATACTGGTTGGGGACGTTTGTCTCGAAAATTGATTAATGGTATTAGGGATAAGCAATCTGGCAAAACAATATTAGATTTTTTGAAATCAGATGGTTTTGCCAATCGCAATTTTATGCAGCTGATCCATGATGATAGTTTGACATTTAAAGAAGACATTCAAAAAGCACAAGTGTCTGGACAAGGCGATAGTTTACATGAACATATTGCAAATTTAGCTGGTAGCCCTGCTATTAAAAAAGGTATTTTACAGACTGTAAAAGTTGTTGATGAATTGGTCAAAGTAATGGGGCGGCATAAGCCAGAAAATATCGTTATTGAAATGGCACGTGAAAATCAGACAACTCAAAAGGGCCAGAAAAATTCGCGAGAGCGTATGAAACGAATCGAAGAAGGTATCAAAGAATTAGGAAGTCAGATTCTTAAAGAGCATCCTGTTGAAAATACTCAATTGCAAAATGAAAAGCTCTATCTCTATTATCTCCAAAATGGAAGAGACATGTATGTGGACCAAGAATTAGATATTAATCGTTTAAGTGATTATGATGTCGATCACATTGTTCCACAAAGTTTCCTTAAAGACGATTCAATAGACAATAAGGTCTTAACGCGTTCTGATAAAAATCGTGGTAAATCGGATAACGTTCCAAGTGAAGAAGTAGTCAAAAAGATGAAAAACTATTGGAGACAACTTCTAAACGCCAAGTTAATCACTCAACGTAAGTTTGATAATTTAACGAAAGCTGAACGTGGAGGTTTGAGTGAACTTGATAAAGCTGGTTTTATCAAACGCCAATTGGTTGAAACTCGCCAAATCACTAAGCATGTGGCACAAATTTTGGATAGTCGCATGAATACTAAATACGATGAAAATGATAAACTTATTCGAGAGGTTAAAGTGATTACCTTAAAATCTAAATTAGTTTCTGACTTCCGAAAAGATTTCCAATTCTATAAAGTACGTGAGATTAACAATTACCATCATGCCCATGATGCGTATCTAAATGCCGTCGTTGGAACTGCTTTGATTAAGAAATATCCAAAACTTGAATCGGAGTTTGTCTATGGTGATTATAAAGTTTATGATGTTCGTAAAATGATTGCTAAGTCTGAGCAAGAAATAGGCAAAGCAACCGCAAAATATTTCTTTTACTCTAATATCATGAACTTCTTCAAAACAGAAATTACACTTGCAAATGGAGAGATTCGCAAACGCCCTCTAATCGAAACTAATGGGGAAACTGGAGAAATTGTCTGGGATAAAGGGCGAGATTTTGCCACAGTGCGCAAAGTATTGTCCATGCCCCAAGTCAATATTGTCAAGAAAACAGAAGTACAGACAGGCGGATTCTCCAAGGAGTCAATTTTACCAAAAAGAAATTCGGACAAGCTTATTGCTCGTAAAAAAGACTGGGATCCAAAAAAATATGGTGGTTTTGATAGTCCAACGGTAGCTTATTCAGTCCTAGTGGTTGCTAAGGTGGAAAAAGGGAAATCGAAGAAGTTAAAATCCGTTAAAGAGTTACTAGGGATCACAATTATGGAAAGAAGTTCCTTTGAAAAAAATCCGATTGACTTTTTAGAAGCTAAAGGATATAAGGAAGTTAAAAAAGACTTAATCATTAAACTACCTAAATATAGTCTTTTTGAGTTAGAAAACGGTCGTAAACGGATGCTGGCTAGTGCCGGAGAATTACAAAAAGGAAATGAGCTGGCTCTGCCAAGCAAATATGTGAATTTTTTATATTTAGCTAGTCATTATGAAAAGTTGAAGGGTAGTCCAGAAGATAACGAACAAAAACAATTGTTTGTGGAGCAGCATAAGCATTATTTAGATGAGATTATTGAGCAAATCAGTGAATTTTCTAAGCGTGTTATTTTAGCAGATGCCAATTTAGATAAAGTTCTTAGTGCATATAACAAACATAGAGACAAACCAATACGTGAACAAGCAGAAAATATTATTCATTTATTTACGTTGACGAATCTTGGAGCTCCCGCTGCTTTTAAATATTTTGATACAACAATTGATCGTAAACGATATACGTCTACAAAAGAAGTTTTAGATGCCACTCTTATCCATCAATCCATCACTGGTCTTTATGAAACACGCATTGATTTGAGTCAGCTAGGAGGTGACTGATAATCAAATGTCAGACGAAAATGCCAATTATTGAAGCGGCTAACGCCGCTTTTTTTGTTTCTGGTCTCCCTTGCTTGTACTTTACAGTATAGCTTCTAGAGATCTGCAGTGACTGGAGCTTCTAGAGATC >pCas9g1-D15-cons (SEQ ID No: 231)GATTAACTAATAAGGAGGGCAAACTACTAGAGATGAGTAAATCCTGGGGCAAATTCATCGAGGAGGAAGAGGCGGAAATGGCTTCCCGTCGTAATCTAATGATTGTCGATGGAACTAACTTAGGCTTTCGCTTCAAACATAACAATAGTAAAAAACCATTTGCCTCAAGTTATGTTTCAACTATTCAATCTCTGGCAAAATCCTACTCTGCCAGAACTACGATTGTTCTAGGTGATAAGGGCAAAAGCGTGTTCAGACTAGAACATCTACCAGAGTATAAAGGTAATCGTGATGAAAAGTACGCACAACGTACGGAAGAGGAGAAAGCGCTAGATGAGCAGTTCTTCGAATACCTCAAAGATGCTTTCGAGTTGTGTAAAACTACATTCCCAACTTTTACCATTCGTGGTGTAGAAGCAGATGACATGGCGGCGTATATTGTTAAGCTCATCGGGCATCTTTATGATCACGTTTGGCTAATATCTACAGATGGTGACTGGGATACTTTATTAACGGATAAAGTTTCTCGTTTTTCTTTCACAACACGTCGTGAGTATCATCTTCGTGATATGTATGAGCACCATAACGTGGACGACGTAGAACAGTTTATCTCCCTGAAAGCAATTATGGGAGATCTAGGAGATAATATTCGTGGTGTTGAAGGAATAGGAGCAAAACGCGGATATAATATTATTCGTGAGTTTGGTAACGTACTGGATATTATTGATCAGCTTCCACTGCCTGGAAAGCAGAAATATATACAGAACCTGAATGCATCGGAAGAACTGCTTTTCCGAAACTTGATTCTGGTTGATTTACCTACCTACTGTGTGGATGCTATTGCTGCTGTAGGTCAAGATGTGTTAGATAAGTTCACGAAAGACATCCTTGAGATCGCGGAACAATGATAAGCTCTTAAAGGGGGTTTTAGATACCAGAGATGGATAAGAAATACTCAATAGGCTTAGATATCGGCACAAATAGCGTCGGATGGGCGGTGATCACTGATGAATATAAGGTTCCGTCTAAAAAGTTCAAGGTTCTGGGAAATACAGACCGCCACAGTATCAAAAAAAATCTTATAGGGGCTCTTTTATTTGACAGTGGAGAGACAGCGGAAGCGACTCGTCTCAAACGGACAGCTCGTAGAAGGTATACACGTCGGAAGAATCGTATTTGTTATCTACAGGAGATTTTTTCAAATGAGATGGCGAAAGTAGATGATAGTTTCTTTCATCGACTTGAAGAGTCTTTTTTGGTGGAAGAAGACAAGAAGCATGAACGTCATCCTATTTTTGGAAATATAGTAGATGAAGTTGCTTATCATGAGAAATATCCAACTATCTATCATCTGCGAAAAAAATTGGTAGATTCTACTGATAAAGCGGATTTGCGCTTAATCTATTTGGCCTTAGCGCATATGATTAAGTTTCGTGGTCATTTTTTGATTGAGGGAGATTTAAATCCTGATAATAGTGATGTGGACAAACTATTTATCCAGTTGGTACAAACCTACAATCAATTATTTGAAGAAAACCCTATTAACGCAAGTGGAGTAGATGCTAAAGCGATTCTTTCTGCACGATTGAGTAAATCAAGACGATTAGAAAATCTCATTGCTCAGCTCCCCGGTGAGAAGAAAAATGGCTTATTTGGGAATCTCATTGCTTTGTCATTGGGTTTGACCCCTAATTTTAAATCAAATTTTGATTTGGCAGAAGATGCTAAATTACAGCTTTCAAAAGATACTTACGATGATGATTTAGATAATTTATTGGCGCAAATTGGAGATCAATATGCTGATTTGTTTTTGGCAGCTAAGAATTTATCAGATGCTATTTTACTTTCAGATATCCTAAGAGTAAATACTGAAATAACTAAGGCTCCCCTATCAGCTTCAATGATTAAACGCTACGATGAACATCATCAAGACTTGACTCTTTTAAAAGCTTTAGTTCGACAACAACTTCCAGAAAAGTATAAAGAAATCTTTTTTGATCAATCAAAAAACGGATATGCAGGTTATATTGATGGGGGAGCTAGCCAAGAAGAATTTTATAAATTTATCAAACCAATTTTAGAAAAAATGGATGGTACTGAGGAATTATTGGTGAAACTAAATCGTGAAGATTTGCTGCGCAAGCAACGGACCTTTGACAACGGCTCTATTCCCCATCAAATTCACTTGGGTGAGCTGCATGCTATTTTGAGAAGACAAGAAGACTTTTATCCATTTTTAAAAGACAATCGTGAGAAGATTGAAAAAATCTTGACTTTTCGAATTCCTTATTATGTTGGTCCATTGGCGCGTGGCAATAGTCGTTTTGCATGGATGACTCGGAAGTCTGAAGAAACAATTACCCCATGGAATTTTGAAGAAGTTGTCGATAAAGGTGCTTCAGCTCAATCATTTATTGAACGCATGACAAACTTTGATAAAAATCTTCCAAATGAAAAAGTACTACCAAAACATAGTTTGCTTTATGAGTATTTTACGGTTTATAACGAATTGACAAAGGTCAAATATGTTACTGAAGGAATGCGAAAACCAGCATTTCTTTCAGGTGAACAGAAGAAAGCCATTGTTGATTTACTCTTCAAAACAAATCGAAAAGTAACCGTTAAGCAATTAAAAGAAGATTATTTCAAAAAAATAGAATGTTTTGATAGTGTTGAAATTTCAGGAGTTGAAGATAGATTTAATGCTTCATTAGGTACCTACCATGATTTGCTAAAAATTATTAAAGATAAAGATTTTTTGGATAATGAAGAAAATGAAGATATCTTAGAGGATATTGTTTTAACATTGACCTTATTTGAAGATAGGGAGATGATTGAGGAAAGACTTAAAACATATGCTCACCTCTTTGATGATAAGGTGATGAAACAGCTTAAACGTCGCCGTTATACTGGTTGGGGACGTTTGTCTCGAAAATTGATTAATGGTATTAGGGATAAGCAATCTGGCAAAACAATATTAGATTTTTTGAAATCAGATGGTTTTGCCAATCGCAATTTTATGCAGCTGATCCATGATGATAGTTTGACATTTAAAGAAGACATTCAAAAAGCACAAGTGTCTGGACAAGGCGATAGTTTACATGAACATATTGCAAATTTAGCTGGTAGCCCTGCTATTAAAAAAGGTATTTTACAGACTGTAAAAGTTGTTGATGAATTGGTCAAAGTAATGGGGCGGCATAAGCCAGAAAATATCGTTATTGAAATGGCACGTGAAAATCAGACAACTCAAAAGGGCCAGAAAAATTCGCGAGAGCGTATGAAACGAATCGAAGAAGGTATCAAAGAATTAGGAAGTCAGATTCTTAAAGAGCATCCTGTTGAAAATACTCAATTGCAAAATGAAAAGCTCTATCTCTATTATCTCCAAAATGGAAGAGACATGTATGTGGACCAAGAATTAGATATTAATCGTTTAAGTGATTATGATGTCGATCACATTGTTCCACAAAGTTTCCTTAAAGACGATTCAATAGACAATAAGGTCTTAACGCGTTCTGATAAAAATCGTGGTAAATCGGATAACGTTCCAAGTGAAGAAGTAGTCAAAAAGATGAAAAACTATTGGAGACAACTTCTAAACGCCAAGTTAATCACTCAACGTAAGTTTGATAATTTAACGAAAGCTGAACGTGGAGGTTTGAGTGAACTTGATAAAGCTGGTTTTATCAAACGCCAATTGGTTGAAACTCGCCAAATCACTAAGCATGTGGCACAAATTTTGGATAGTCGCATGAATACTAAATACGATGAAAATGATAAACTTATTCGAGAGGTTAAAGTGATTACCTTAAAATCTAAATTAGTTTCTGACTTCCGAAAAGATTTCCAATTCTATAAAGTACGTGAGATTAACAATTACCATCATGCCCATGATGCGTATCTAAATGCCGTCGTTGGAACTGCTTTGATTAAGAAATATCCAAAACTTGAATCGGAGTTTGTCTATGGTGATTATAAAGTTTATGATGTTCGTAAAATGATTGCTAAGTCTGAGCAAGAAATAGGCAAAGCAACCGCAAAATATTTCTTTTACTCTAATATCATGAACTTCTTCAAAACAGAAATTACACTTGCAAATGGAGAGATTCGCAAACGCCCTCTAATCGAAACTAATGGGGAAACTGGAGAAATTGTCTGGGATAAAGGGCGAGATTTTGCCACAGTGCGCAAAGTATTGTCCATGCCCCAAGTCAATATTGTCAAGAAAACAGAAGTACAGACAGGCGGATTCTCCAAGGAGTCAATTTTACCAAAAAGAAATTCGGACAAGCTTATTGCTCGTAAAAAAGACTGGGATCCAAAAAAATATGGTGGTTTTGATAGTCCAACGGTAGCTTATTCAGTCCTAGTGGTTGCTAAGGTGGAAAAAGGGAAATCGAAGAAGTTAAAATCCGTTAAAGAGTTACTAGGGATCACAATTATGGAAAGAAGTTCCTTTGAAAAAAATCCGATTGACTTTTTAGAAGCTAAAGGATATAAGGAAGTTAAAAAAGACTTAATCATTAAACTACCTAAATATAGTCTTTTTGAGTTAGAAAACGGTCGTAAACGGATGCTGGCTAGTGCCGGAGAATTACAAAAAGGAAATGAGCTGGCTCTGCCAAGCAAATATGTGAATTTTTTATATTTAGCTAGTCATTATGAAAAGTTGAAGGGTAGTCCAGAAGATAACGAACAAAAACAATTGTTTGTGGAGCAGCATAAGCATTATTTAGATGAGATTATTGAGCAAATCAGTGAATTTTCTAAGCGTGTTATTTTAGCAGATGCCAATTTAGATAAAGTTCTTAGTGCATATAACAAACATAGAGACAAACCAATACGTGAACAAGCAGAAAATATTATTCATTTATTTACGTTGACGAATCTTGGAGCTCCCGCTGCTTTTAAATATTTTGATACAACAATTGATCGTAAACGATATACGTCTACAAAAGAAGTTTTAGATGCCACTCTTATCCATCAATCCATCACTGGTCTTTATGAAACACGCATTGATTTGAGTCAGCTAGGAGGTGACTGATAATCAAATGTCAGACGAAAATGCCAATTATTGAAGCGGCTAACGCCGCTTTTTTTGTTTCTGGTCTCCCTTGCTTGTACTTTACAGTATAGCTTCTAGAGATCTGCAGTGACTGGAGCTTCTAGAGATCTGCAGTGACTGGGAAAACCCTGGCGACTAGTCTTGGACTCCTGTTGATAGATCCAGTAATGACCTCAGAACTCCATCTGGATTTGTTCAGAACGCTCGGTTGCCGCCGGGCGTTTTTTATTGGTGAGAATCCAGGGGTCCCCAATAATTACGATTTAAATCCTTCAAACTTCCCAAAGGCGAGCCCTAGTGACATTAGAAAACCGACTGTAAAAAGTACAGTCGGCATTATCTCATATTATAAAAGCCAGTCATTAGGCCTATCTGACAATTCCTGAATAGAGTTCATAAACAATCCTGCATGATAACCATCACAAACAGAATGATGTACCTGTAAAGATAGCGGTAAATATATTGAATTACCTTTATTAATGAATTTTCCTGCTGTAATAATGGGTAGAAGGTAATTACTATTATTATTGATATTTAAGTTAAACCCAGTAAATGAAGTCCATGGAATAATAGAAAGAGAAAAAGCATTTTCAGGTATAGGTGTTTTGGGAAACAATTTCCCCGAACCATTATATTTCTCTACATCAGAAAGGTATAAATCATAAAACTCTTTGAAGTCATTCTTTACAGGAGTCCAAATACCAGAGAATGTTTTAGATACACCATCAAAAATTGTATAAAGTGGCTCTAACTTATCCCAATAACCTAACTCTCCGTCGCTATTGTAACCAGTTCTAAAAGCTGTATTTGAGTTTATCACCCTTGTCACTAAGAAAATAAATGCAGGGTAAAATTTATATCCTTCTTGTTTTATGTTTCGGTATAAAACACTAATATCAATTTCTGTGGTTATACTAAAAGTCGTTTGTTGGTTCAAATAATGATTAAATATCTCTTTTCTCTTCCAATTGTCTAAATCAATTTTATTAAAGTTCATTTGATATGCCTCCTAAATTTTTATCTAAAGTGAATTTAGGAGGCTTACTTGTCTGCTTTCTTCATTAGAATCAATCCTTTTTTAAAAGTCAATCCCGTTTGTTGAAGACTTTTGTCCTTTTCCGCTGCATAAACAATATGGCCCGTTTGTTGAACTACTCTTTAATAAAATAATTTTTCCGTTCCCAATTCCACATTGCAATAATAGAAAATCCATCTTCATCGGCTTTTTCGTCATCATCTGTATGAATCAAATCGCCTTCTTCTGTGTCATCAAGGTTTAATTTTTTATGTATTTCTTTTAACAAACCACCATAGGAGATTAACCTTTTACGGTGTAAACCTTCCTCCAAATCAGACAAACGTTTCAAATTCTTTTCTTCATCATCGGTCATAAAATCCGTATCCTTTACAGGATATTTTGCAGTTTCGTCAATTGCCGATTGTATATCCGATTTATATTTATTTTTCGGTCGAATCATTTGAACTTTTACATTTGGATCATAGTCTAATTTCATTGCCTTTTTCCAAAATTGAATCCATTGTTTTTGATTCACGTAGTTTTCTGTATTCTTAAAATAAGTTGGTTCCACACATACCAATACATGCATGTGCTGATTATAAGAATTATCTTTATTATTTATTGTCACTTCCGTTGCACGCATAAAACCAACAAGATTTTTATTAATTTTTTTATATTGCATCATTCGGCGAAATCCTTGAGCCATATCTGACAAACTCTTATTTAATTCTTCGCCATCATAAACATTTTTAACTGTTAATGTGAGAAACAACCAACGAACTGTTGGCTTTTGTTTAATAACTTCAGCAACAACCTTTTGTGACTGAATGCCATGTTTCATTGCTCTCCTCCAGTTGCACATTGGACAAAGCCTGGATTTACAAAACCACACTCGATACAACTTTCTTTCGCCTGTTTCACGATTTTGTTTATACTCTAATATTTCAGCACAATCTTTTACTCTTTCAGCCTTTTTAAATTCAAGAATATGCAGAAGTTCAAAGTAATCAACATTAGCGATTTTCTTTTCTCTCCATGGTCTCACTTTTCCACTTTTTGTCTTGTCCACTAAAACCCTTGATTTTTCATCTGAATAAATGCTACTATTAGGACACATAATATTAAAAGAAACCCCCATCTATTTAGTTATTTGTTTGGTCACTTATAACTTTAACAGATGGGGTTTTTCTGTGCAACCAATTTTAAGGGTTTTCCAATACTTTAAAACACATACATACCAACACTTCAACGCACCTTTCAGCAACTAAAATAAAAATGACGTTATTTCTATATGTATCAAGATAAGAAAGAACAAGTTCAAAACCATCAAAAAAAGACACCTTTTCAGGTGCTTTTTTTATTTTATAAACTCATTCCCTGATCTCGACTTCGTTCTTTTTTTACCTCTCGGTTATGAGTTAGTTCAAATTCGTTCTTTTTAGGTTCTAAATCGTGTTTTTCTTGGAATTGTGCTGTTTTATCCTTTACCTTGTCTACAAACCCCTTAAAAACGTTTTTAAAGGCTTTTAAGCGTCTGTACGTTCCTTAAGGAATTATTCCTTAGTGCTTTCTAGGTTAATGTCATGATAATAATGGTTTCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTCCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTGTTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGCAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCTTAATAAGATGATCTTCTTGAGATCGTTTTGGTCTGCGCGTAATCTCTTGCTCTGAAAACGAAAAAACCGCCTTGCAGGGAGGTTTTTCGAAGGTTCTCTGAGCTACCAACTCTTTGAACCGAGGTAACTGGCTTGCAGGAGCGCAGTCACCAAAACTTGTCCTTTCAGTTTAGCCTTAACCGGCGCATGACTTCAAGACTAACTCCTCTAAATCAATTACCAGTGGCTGCTGCCAGTGGTGCTTTTGCATGTCTTTCCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGACTGAACGGGGGGTTCGTGCATACAGTCCAGCTTGGAGCGAACTGCCTACCCGGAACTGAGTGTCAGGCGTGGAATGAGACAAACGCGGCCATAACAGCGGAATGACACCGGTAAACCGAAAGGCAGGAACAGGAGAGCGCACGAGGGAGCCGCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCACTGATTTGAGCGTCAGATTTCGTGATGCTTGTCAGGGGGCGGAGCCTATGGAAAAACGCTTTGCCCGAGCCTATGGAAAAACGCTTTGCCCCACACAGGCTCTTGAACAAGGGATAACAATTTGTCATAGCTGTATTCGTTACAAGGAGGATTTTCGAAAAAACACCCTAACGGGTGTTTTTTTATAGCTGGTCTCCCCAAGTGCTGTAAAAAACGCCGAATGAAGCGGATGAAATTGCTCATCGTCTCGTGAAAAAGCCGAAGAAGGTTAAGCCTGGGTATAAAAAGAAAATGAGCTATGAGATGGAGAAAGCCATAACCATGAGTGATAACACTGGTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTTTTTTTCTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCCTCAATGATCTCCTTATCCGGTTAAGATGGCAAGCTTGACAAGTATTTCTTCAGAATTTACAATGAAGTTTACATGAC >pCas9g2-D15-cons (SEQ ID No: 232)GATTAACTAATAAGGAGGGCAAACTACTAGAGATGAGTAAATCCTGGGGCAAATTCATCGAGGAGGAAGAGGCGGAAATGGCTTCCCGTCGTAATCTAATGATTGTCGATGGAACTAACTTAGGCTTTCGCTTCAAACATAACAATAGTAAAAAACCATTTGCCTCAAGTTATGTTTCAACTATTCAATCTCTGGCAAAATCCTACTCTGCCAGAACTACGATTGTTCTAGGTGATAAGGGCAAAAGCGTGTTCAGACTAGAACATCTACCAGAGTATAAAGGTAATCGTGATGAAAAGTACGCACAACGTACGGAAGAGGAGAAAGCGCTAGATGAGCAGTTCTTCGAATACCTCAAAGATGCTTTCGAGTTGTGTAAAACTACATTCCCAACTTTTACCATTCGTGGTGTAGAAGCAGATGACATGGCGGCGTATATTGTTAAGCTCATCGGGCATCTTTATGATCACGTTTGGCTAATATCTACAGATGGTGACTGGGATACTTTATTAACGGATAAAGTTTCTCGTTTTTCTTTCACAACACGTCGTGAGTATCATCTTCGTGATATGTATGAGCACCATAACGTGGACGACGTAGAACAGTTTATCTCCCTGAAAGCAATTATGGGAGATCTAGGAGATAATATTCGTGGTGTTGAAGGAATAGGAGCAAAACGCGGATATAATATTATTCGTGAGTTTGGTAACGTACTGGATATTATTGATCAGCTTCCACTGCCTGGAAAGCAGAAATATATACAGAACCTGAATGCATCGGAAGAACTGCTTTTCCGAAACTTGATTCTGGTTGATTTACCTACCTACTGTGTGGATGCTATTGCTGCTGTAGGTCAAGATGTGTTAGATAAGTTCACGAAAGACATCCTTGAGATCGCGGAACAATGATAAGCTCTTAAAGGGGGTTTTAGATACCAGAGATGGATAAGAAATACTCAATAGGCTTAGATATCGGCACAAATAGCGTCGGATGGGCGGTGATCACTGATGAATATAAGGTTCCGTCTAAAAAGTTCAAGGTTCTGGGAAATACAGACCGCCACAGTATCAAAAAAAATCTTATAGGGGCTCTTTTATTTGACAGTGGAGAGACAGCGGAAGCGACTCGTCTCAAACGGACAGCTCGTAGAAGGTATACACGTCGGAAGAATCGTATTTGTTATCTACAGGAGATTTTTTCAAATGAGATGGCGAAAGTAGATGATAGTTTCTTTCATCGACTTGAAGAGTCTTTTTTGGTGGAAGAAGACAAGAAGCATGAACGTCATCCTATTTTTGGAAATATAGTAGATGAAGTTGCTTATCATGAGAAATATCCAACTATCTATCATCTGCGAAAAAAATTGGTAGATTCTACTGATAAAGCGGATTTGCGCTTAATCTATTTGGCCTTAGCGCATATGATTAAGTTTCGTGGTCATTTTTTGATTGAGGGAGATTTAAATCCTGATAATAGTGATGTGGACAAACTATTTATCCAGTTGGTACAAACCTACAATCAATTATTTGAAGAAAACCCTATTAACGCAAGTGGAGTAGATGCTAAAGCGATTCTTTCTGCACGATTGAGTAAATCAAGACGATTAGAAAATCTCATTGCTCAGCTCCCCGGTGAGAAGAAAAATGGCTTATTTGGGAATCTCATTGCTTTGTCATTGGGTTTGACCCCTAATTTTAAATCAAATTTTGATTTGGCAGAAGATGCTAAATTACAGCTTTCAAAAGATACTTACGATGATGATTTAGATAATTTATTGGCGCAAATTGGAGATCAATATGCTGATTTGTTTTTGGCAGCTAAGAATTTATCAGATGCTATTTTACTTTCAGATATCCTAAGAGTAAATACTGAAATAACTAAGGCTCCCCTATCAGCTTCAATGATTAAACGCTACGATGAACATCATCAAGACTTGACTCTTTTAAAAGCTTTAGTTCGACAACAACTTCCAGAAAAGTATAAAGAAATCTTTTTTGATCAATCAAAAAACGGATATGCAGGTTATATTGATGGGGGAGCTAGCCAAGAAGAATTTTATAAATTTATCAAACCAATTTTAGAAAAAATGGATGGTACTGAGGAATTATTGGTGAAACTAAATCGTGAAGATTTGCTGCGCAAGCAACGGACCTTTGACAACGGCTCTATTCCCCATCAAATTCACTTGGGTGAGCTGCATGCTATTTTGAGAAGACAAGAAGACTTTTATCCATTTTTAAAAGACAATCGTGAGAAGATTGAAAAAATCTTGACTTTTCGAATTCCTTATTATGTTGGTCCATTGGCGCGTGGCAATAGTCGTTTTGCATGGATGACTCGGAAGTCTGAAGAAACAATTACCCCATGGAATTTTGAAGAAGTTGTCGATAAAGGTGCTTCAGCTCAATCATTTATTGAACGCATGACAAACTTTGATAAAAATCTTCCAAATGAAAAAGTACTACCAAAACATAGTTTGCTTTATGAGTATTTTACGGTTTATAACGAATTGACAAAGGTCAAATATGTTACTGAAGGAATGCGAAAACCAGCATTTCTTTCAGGTGAACAGAAGAAAGCCATTGTTGATTTACTCTTCAAAACAAATCGAAAAGTAACCGTTAAGCAATTAAAAGAAGATTATTTCAAAAAAATAGAATGTTTTGATAGTGTTGAAATTTCAGGAGTTGAAGATAGATTTAATGCTTCATTAGGTACCTACCATGATTTGCTAAAAATTATTAAAGATAAAGATTTTTTGGATAATGAAGAAAATGAAGATATCTTAGAGGATATTGTTTTAACATTGACCTTATTTGAAGATAGGGAGATGATTGAGGAAAGACTTAAAACATATGCTCACCTCTTTGATGATAAGGTGATGAAACAGCTTAAACGTCGCCGTTATACTGGTTGGGGACGTTTGTCTCGAAAATTGATTAATGGTATTAGGGATAAGCAATCTGGCAAAACAATATTAGATTTTTTGAAATCAGATGGTTTTGCCAATCGCAATTTTATGCAGCTGATCCATGATGATAGTTTGACATTTAAAGAAGACATTCAAAAAGCACAAGTGTCTGGACAAGGCGATAGTTTACATGAACATATTGCAAATTTAGCTGGTAGCCCTGCTATTAAAAAAGGTATTTTACAGACTGTAAAAGTTGTTGATGAATTGGTCAAAGTAATGGGGCGGCATAAGCCAGAAAATATCGTTATTGAAATGGCACGTGAAAATCAGACAACTCAAAAGGGCCAGAAAAATTCGCGAGAGCGTATGAAACGAATCGAAGAAGGTATCAAAGAATTAGGAAGTCAGATTCTTAAAGAGCATCCTGTTGAAAATACTCAATTGCAAAATGAAAAGCTCTATCTCTATTATCTCCAAAATGGAAGAGACATGTATGTGGACCAAGAATTAGATATTAATCGTTTAAGTGATTATGATGTCGATCACATTGTTCCACAAAGTTTCCTTAAAGACGATTCAATAGACAATAAGGTCTTAACGCGTTCTGATAAAAATCGTGGTAAATCGGATAACGTTCCAAGTGAAGAAGTAGTCAAAAAGATGAAAAACTATTGGAGACAACTTCTAAACGCCAAGTTAATCACTCAACGTAAGTTTGATAATTTAACGAAAGCTGAACGTGGAGGTTTGAGTGAACTTGATAAAGCTGGTTTTATCAAACGCCAATTGGTTGAAACTCGCCAAATCACTAAGCATGTGGCACAAATTTTGGATAGTCGCATGAATACTAAATACGATGAAAATGATAAACTTATTCGAGAGGTTAAAGTGATTACCTTAAAATCTAAATTAGTTTCTGACTTCCGAAAAGATTTCCAATTCTATAAAGTACGTGAGATTAACAATTACCATCATGCCCATGATGCGTATCTAAATGCCGTCGTTGGAACTGCTTTGATTAAGAAATATCCAAAACTTGAATCGGAGTTTGTCTATGGTGATTATAAAGTTTATGATGTTCGTAAAATGATTGCTAAGTCTGAGCAAGAAATAGGCAAAGCAACCGCAAAATATTTCTTTTACTCTAATATCATGAACTTCTTCAAAACAGAAATTACACTTGCAAATGGAGAGATTCGCAAACGCCCTCTAATCGAAACTAATGGGGAAACTGGAGAAATTGTCTGGGATAAAGGGCGAGATTTTGCCACAGTGCGCAAAGTATTGTCCATGCCCCAAGTCAATATTGTCAAGAAAACAGAAGTACAGACAGGCGGATTCTCCAAGGAGTCAATTTTACCAAAAAGAAATTCGGACAAGCTTATTGCTCGTAAAAAAGACTGGGATCCAAAAAAATATGGTGGTTTTGATAGTCCAACGGTAGCTTATTCAGTCCTAGTGGTTGCTAAGGTGGAAAAAGGGAAATCGAAGAAGTTAAAATCCGTTAAAGAGTTACTAGGGATCACAATTATGGAAAGAAGTTCCTTTGAAAAAAATCCGATTGACTTTTTAGAAGCTAAAGGATATAAGGAAGTTAAAAAAGACTTAATCATTAAACTACCTAAATATAGTCTTTTTGAGTTAGAAAACGGTCGTAAACGGATGCTGGCTAGTGCCGGAGAATTACAAAAAGGAAATGAGCTGGCTCTGCCAAGCAAATATGTGAATTTTTTATATTTAGCTAGTCATTATGAAAAGTTGAAGGGTAGTCCAGAAGATAACGAACAAAAACAATTGTTTGTGGAGCAGCATAAGCATTATTTAGATGAGATTATTGAGCAAATCAGTGAATTTTCTAAGCGTGTTATTTTAGCAGATGCCAATTTAGATAAAGTTCTTAGTGCATATAACAAACATAGAGACAAACCAATACGTGAACAAGCAGAAAATATTATTCATTTATTTACGTTGACGAATCTTGGAGCTCCCGCTGCTTTTAAATATTTTGATACAACAATTGATCGTAAACGATATACGTCTACAAAAGAAGTTTTAGATGCCACTCTTATCCATCAATCCATCACTGGTCTTTATGAAACACGCATTGATTTGAGTCAGCTAGGAGGTGACTGATAATCAAATGTCAGACGAAAATGCCAATTATTGAAGCGGCTAACGCCGCTTTTTTTGTTTCTGGTCTCCCTTGCTTGTACTTTACAGTATAGCTTCTAGAGATCTGCAGTGACTGGAGCTTCTAGAGATCAGGTCAGACGCGATTTCCTGGGTGCTCGAGCCATGGGAAAGCGGTGGTGGAAAAAACGCCGAATGAAGCGGATGAAATTGCTCATCGTCTCGTGAAAAAGCCGAAGAAGGTTAAGCCTGGGTATAAAAAGAAAATGAGCTATGAGATGGAGAAATTGAAGTCATGCGCCGGTTAGTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTTTTTTTCTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCCTCAATGATCCGACAGGAAGTGGTATTAGCGACTCCTACAAGGAATAGGTGTCTGGGTCATGCAGTGACTGGGAAAACCCTGGCGACTAGTCTTGGACTCCTGTTGATAGATCCAGTAATGACCTCAGAACTCCATCTGGATTTGTTCAGAACGCTCGGTTGCCGCCGGGCGTTTTTTATTGGTGAGAATCCAGGGGTCCCCAATAATTACGATTTAAATCCTTCAAACTTCCCAAAGGCGAGCCCTAGTGACATTAGAAAACCGACTGTAAAAAGTACAGTCGGCATTATCTCATATTATAAAAGCCAGTCATTAGGCCTATCTGACAATTCCTGAATAGAGTTCATAAACAATCCTGCATGATAACCATCACAAACAGAATGATGTACCTGTAAAGATAGCGGTAAATATATTGAATTACCTTTATTAATGAATTTTCCTGCTGTAATAATGGGTAGAAGGTAATTACTATTATTATTGATATTTAAGTTAAACCCAGTAAATGAAGTCCATGGAATAATAGAAAGAGAAAAAGCATTTTCAGGTATAGGTGTTTTGGGAAACAATTTCCCCGAACCATTATATTTCTCTACATCAGAAAGGTATAAATCATAAAACTCTTTGAAGTCATTCTTTACAGGAGTCCAAATACCAGAGAATGTTTTAGATACACCATCAAAAATTGTATAAAGTGGCTCTAACTTATCCCAATAACCTAACTCTCCGTCGCTATTGTAACCAGTTCTAAAAGCTGTATTTGAGTTTATCACCCTTGTCACTAAGAAAATAAATGCAGGGTAAAATTTATATCCTTCTTGTTTTATGTTTCGGTATAAAACACTAATATCAATTTCTGTGGTTATACTAAAAGTCGTTTGTTGGTTCAAATAATGATTAAATATCTCTTTTCTCTTCCAATTGTCTAAATCAATTTTATTAAAGTTCATTTGATATGCCTCCTAAATTTTTATCTAAAGTGAATTTAGGAGGCTTACTTGTCTGCTTTCTTCATTAGAATCAATCCTTTTTTAAAAGTCAATCCCGTTTGTTGAAGACTTTTGTCCTTTTCCGCTGCATAAACAATATGGCCCGTTTGTTGAACTACTCTTTAATAAAATAATTTTTCCGTTCCCAATTCCACATTGCAATAATAGAAAATCCATCTTCATCGGCTTTTTCGTCATCATCTGTATGAATCAAATCGCCTTCTTCTGTGTCATCAAGGTTTAATTTTTTATGTATTTCTTTTAACAAACCACCATAGGAGATTAACCTTTTACGGTGTAAACCTTCCTCCAAATCAGACAAACGTTTCAAATTCTTTTCTTCATCATCGGTCATAAAATCCGTATCCTTTACAGGATATTTTGCAGTTTCGTCAATTGCCGATTGTATATCCGATTTATATTTATTTTTCGGTCGAATCATTTGAACTTTTACATTTGGATCATAGTCTAATTTCATTGCCTTTTTCCAAAATTGAATCCATTGTTTTTGATTCACGTAGTTTTCTGTATTCTTAAAATAAGTTGGTTCCACACATACCAATACATGCATGTGCTGATTATAAGAATTATCTTTATTATTTATTGTCACTTCCGTTGCACGCATAAAACCAACAAGATTTTTATTAATTTTTTTATATTGCATCATTCGGCGAAATCCTTGAGCCATATCTGACAAACTCTTATTTAATTCTTCGCCATCATAAACATTTTTAACTGTTAATGTGAGAAACAACCAACGAACTGTTGGCTTTTGTTTAATAACTTCAGCAACAACCTTTTGTGACTGAATGCCATGTTTCATTGCTCTCCTCCAGTTGCACATTGGACAAAGCCTGGATTTACAAAACCACACTCGATACAACTTTCTTTCGCCTGTTTCACGATTTTGTTTATACTCTAATATTTCAGCACAATCTTTTACTCTTTCAGCCTTTTTAAATTCAAGAATATGCAGAAGTTCAAAGTAATCAACATTAGCGATTTTCTTTTCTCTCCATGGTCTCACTTTTCCACTTTTTGTCTTGTCCACTAAAACCCTTGATTTTTCATCTGAATAAATGCTACTATTAGGACACATAATATTAAAAGAAACCCCCATCTATTTAGTTATTTGTTTGGTCACTTATAACTTTAACAGATGGGGTTTTTCTGTGCAACCAATTTTAAGGGTTTTCCAATACTTTAAAACACATACATACCAACACTTCAACGCACCTTTCAGCAACTAAAATAAAAATGACGTTATTTCTATATGTATCAAGATAAGAAAGAACAAGTTCAAAACCATCAAAAAAAGACACCTTTTCAGGTGCTTTTTTTATTTTATAAACTCATTCCCTGATCTCGACTTCGTTCTTTTTTTACCTCTCGGTTATGAGTTAGTTCAAATTCGTTCTTTTTAGGTTCTAAATCGTGTTTTTCTTGGAATTGTGCTGTTTTATCCTTTACCTTGTCTACAAACCCCTTAAAAACGTTTTTAAAGGCTTTTAAGCGTCTGTACGTTCCTTAAGGAATTATTCCTTAGTGCTTTCTAGGTTAATGTCATGATAATAATGGTTTCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTCCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTGTTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGCAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCTTAATAAGATGATCTTCTTGAGATCGTTTTGGTCTGCGCGTAATCTCTTGCTCTGAAAACGAAAAAACCGCCTTGCAGGGAGGTTTTTCGAAGGTTCTCTGAGCTACCAACTCTTTGAACCGAGGTAACTGGCTTGCAGGAGCGCAGTCACCAAAACTTGTCCTTTCAGTTTAGCCTTAACCGGCGCATGACTTCAAGACTAACTCCTCTAAATCAATTACCAGTGGCTGCTGCCAGTGGTGCTTTTGCATGTCTTTCCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGACTGAACGGGGGGTTCGTGCATACAGTCCAGCTTGGAGCGAACTGCCTACCCGGAACTGAGTGTCAGGCGTGGAATGAGACAAACGCGGCCATAACAGCGGAATGACACCGGTAAACCGAAAGGCAGGAACAGGAGAGCGCACGAGGGAGCCGCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCACTGATTTGAGCGTCAGATTTCGTGATGCTTGTCAGGGGGCGGAGCCTATGGAAAAACGCTTTGCCCGAGCCTATGGAAAAACGCTTTGCCCCACACAGGCTCTTGAACAAGGGATAACAATTTGTCATAGCTGTATTCGTTACAAGGAGGATTTTCGAAAAAACACCCTAACGGGTGTTTTTTTATAGCTGGTCTCCCCAAGTGCTGTAAAAAACGCCGAATGAAGCGGATGAAATTGCTCATCGTCTCGTGAAAAAGCCGAAGAAGGTTAAGCCTGGGTATAAAAAGAAAATGAGCTATGAGATGGAGAAAGCCATAACCATGAGTGATAACACTGGTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTTTTTTTCTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCCTCAATGATCTCCTTATCCGGTTAAGATGGCAAGCTTGACAAGTATTTCTTCAGAATTTACAATGAAGTTTACATGAC >pCas9g1 (SEQ ID No: 233)tccttatccggttaagatggCTTTTAAATCAATTTTCAGCTCCTGTATACAATTACCAAAGTTTTTCTGAATGAAGCCATGTGTTTTGACACATTCTATACTCACAAGGAGGTGAGACACatggataagaaatactcaataggctTAGATATCGGCACAAATAGCGTCGGATGGGCGGTGATCACTGATGAATATAAGGTTCCGTCTAAAAAGTTCAAGGTTCTGGGAAATACAGACCGCCACAGTATCAAAAAAAATCTTATAGGGGCTCTTTTATTTGACAGTGGAGAGACAGCGGAAGCGACTCGTCTCAAACGGACAGCTCGTAGAAGGTATACACGTCGGAAGAATCGTATTTGTTATCTACAGGAGATTTTTTCAAATGAGATGGCGAAAGTAGATGATAGTTTCTTTCATCGACTTGAAGAGTCTTTTTTGGTGGAAGAAGACAAGAAGCATGAACGTCATCCTATTTTTGGAAATATAGTAGATGAAGTTGCTTATCATGAGAAATATCCAACTATCTATCATCTGCGAAAAAAATTGGTAGATTCTACTGATAAAGCGGATTTGCGCTTAATCTATTTGGCCTTAGCGCATATGATTAAGTTTCGTGGTCATTTTTTGATTGAGGGAGATTTAAATCCTGATAATAGTGATGTGGACAAACTATTTATCCAGTTGGTACAAACCTACAATCAATTATTTGAAGAAAACCCTATTAACGCAAGTGGAGTAGATGCTAAAGCGATTCTTTCTGCACGATTGAGTAAATCAAGACGATTAGAAAATCTCATTGCTCAGCTCCCCGGTGAGAAGAAAAATGGCTTATTTGGGAATCTCATTGCTTTGTCATTGGGTTTGACCCCTAATTTTAAATCAAATTTTGATTTGGCAGAAGATGCTAAATTACAGCTTTCAAAAGATACTTACGATGATGATTTAGATAATTTATTGGCGCAAATTGGAGATCAATATGCTGATTTGTTTTTGGCAGCTAAGAATTTATCAGATGCTATTTTACTTTCAGATATCCTAAGAGTAAATACTGAAATAACTAAGGCTCCCCTATCAGCTTCAATGATTAAACGCTACGATGAACATCATCAAGACTTGACTCTTTTAAAAGCTTTAGTTCGACAACAACTTCCAGAAAAGTATAAAGAAATCTTTTTTGATCAATCAAAAAACGGATATGCAGGTTATATTGATGGGGGAGCTAGCCAAGAAGAATTTTATAAATTTATCAAACCAATTTTAGAAAAAATGGATGGTACTGAGGAATTATTGGTGAAACTAAATCGTGAAGATTTGCTGCGCAAGCAACGGACCTTTGACAACGGCTCTATTCCCCATCAAATTCACTTGGGTGAGCTGCATGCTATTTTGAGAAGACAAGAAGACTTTTATCCATTTTTAAAAGACAATCGTGAGAAGATTGAAAAAATCTTGACTTTTCGAATTCCTTATTATGTTGGTCCATTGGCGCGTGGCAATAGTCGTTTTGCATGGATGACTCGGAAGTCTGAAGAAACAATTACCCCATGGAATTTTGAAGAAGTTGTCGATAAAGGTGCTTCAGCTCAATCATTTATTGAACGCATGACAAACTTTGATAAAAATCTTCCAAATGAAAAAGTACTACCAAAACATAGTTTGCTTTATGAGTATTTTACGGTTTATAACGAATTGACAAAGGTCAAATATGTTACTGAAGGAATGCGAAAACCAGCATTTCTTTCAGGTGAACAGAAGAAAGCCATTGTTGATTTACTCTTCAAAACAAATCGAAAAGTAACCGTTAAGCAATTAAAAGAAGATTATTTCAAAAAAATAGAATGTTTTGATAGTGTTGAAATTTCAGGAGTTGAAGATAGATTTAATGCTTCATTAGGTACCTACCATGATTTGCTAAAAATTATTAAAGATAAAGATTTTTTGGATAATGAAGAAAATGAAGATATCTTAGAGGATATTGTTTTAACATTGACCTTATTTGAAGATAGGGAGATGATTGAGGAAAGACTTAAAACATATGCTCACCTCTTTGATGATAAGGTGATGAAACAGCTTAAACGTCGCCGTTATACTGGTTGGGGACGTTTGTCTCGAAAATTGATTAATGGTATTAGGGATAAGCAATCTGGCAAAACAATATTAGATTTTTTGAAATCAGATGGTTTTGCCAATCGCAATTTTATGCAGCTGATCCATGATGATAGTTTGACATTTAAAGAAGACATTCAAAAAGCACAAGTGTCTGGACAAGGCGATAGTTTACATGAACATATTGCAAATTTAGCTGGTAGCCCTGCTATTAAAAAAGGTATTTTACAGACTGTAAAAGTTGTTGATGAATTGGTCAAAGTAATGGGGCGGCATAAGCCAGAAAATATCGTTATTGAAATGGCACGTGAAAATCAGACAACTCAAAAGGGCCAGAAAAATTCGCGAGAGCGTATGAAACGAATCGAAGAAGGTATCAAAGAATTAGGAAGTCAGATTCTTAAAGAGCATCCTGTTGAAAATACTCAATTGCAAAATGAAAAGCTCTATCTCTATTATCTCCAAAATGGAAGAGACATGTATGTGGACCAAGAATTAGATATTAATCGTTTAAGTGATTATGATGTCGATCACATTGTTCCACAAAGTTTCCTTAAAGACGATTCAATAGACAATAAGGTCTTAACGCGTTCTGATAAAAATCGTGGTAAATCGGATAACGTTCCAAGTGAAGAAGTAGTCAAAAAGATGAAAAACTATTGGAGACAACTTCTAAACGCCAAGTTAATCACTCAACGTAAGTTTGATAATTTAACGAAAGCTGAACGTGGAGGTTTGAGTGAACTTGATAAAGCTGGTTTTATCAAACGCCAATTGGTTGAAACTCGCCAAATCACTAAGCATGTGGCACAAATTTTGGATAGTCGCATGAATACTAAATACGATGAAAATGATAAACTTATTCGAGAGGTTAAAGTGATTACCTTAAAATCTAAATTAGTTTCTGACTTCCGAAAAGATTTCCAATTCTATAAAGTACGTGAGATTAACAATTACCATCATGCCCATGATGCGTATCTAAATGCCGTCGTTGGAACTGCTTTGATTAAGAAATATCCAAAACTTGAATCGGAGTTTGTCTATGGTGATTATAAAGTTTATGATGTTCGTAAAATGATTGCTAAGTCTGAGCAAGAAATAGGCAAAGCAACCGCAAAATATTTCTTTTACTCTAATATCATGAACTTCTTCAAAACAGAAATTACACTTGCAAATGGAGAGATTCGCAAACGCCCTCTAATCGAAACTAATGGGGAAACTGGAGAAATTGTCTGGGATAAAGGGCGAGATTTTGCCACAGTGCGCAAAGTATTGTCCATGCCCCAAGTCAATATTGTCAAGAAAACAGAAGTACAGACAGGCGGATTCTCCAAGGAGTCAATTTTACCAAAAAGAAATTCGGACAAGCTTATTGCTCGTAAAAAAGACTGGGATCCAAAAAAATATGGTGGTTTTGATAGTCCAACGGTAGCTTATTCAGTCCTAGTGGTTGCTAAGGTGGAAAAAGGGAAATCGAAGAAGTTAAAATCCGTTAAAGAGTTACTAGGGATCACAATTATGGAAAGAAGTTCCTTTGAAAAAAATCCGATTGACTTTTTAGAAGCTAAAGGATATAAGGAAGTTAAAAAAGACTTAATCATTAAACTACCTAAATATAGTCTTTTTGAGTTAGAAAACGGTCGTAAACGGATGCTGGCTAGTGCCGGAGAATTACAAAAAGGAAATGAGCTGGCTCTGCCAAGCAAATATGTGAATTTTTTATATTTAGCTAGTCATTATGAAAAGTTGAAGGGTAGTCCAGAAGATAACGAACAAAAACAATTGTTTGTGGAGCAGCATAAGCATTATTTAGATGAGATTATTGAGCAAATCAGTGAATTTTCTAAGCGTGTTATTTTAGCAGATGCCAATTTAGATAAAGTTCTTAGTGCATATAACAAACATAGAGACAAACCAATACGTGAACAAGCAGAAAATATTATTCATTTATTTACGTTGACGAATCTTGGAGCTCCCGCTGCTTTTAAATATTTTGATACAACAATTGATCGTAAACGATATACGTCTACAAAAGAAGTTTTAGATGCCACTCTTATCCATCAATCCATCACTGGTCTTTATGAAACACGCATTGATTTGAGTCAGCTAGGAGGTGACTGATAATCAAATGTCAGACGAAAATGCCAATTATTGAAGCGGCTAACGCCGCTTTTTTTGTTTCTGGTCTCCCTTGCTTGTACTTTACAGTATAGCTTCTAGAGATCTGCAGTGACTGGAGCTTCTAGAGATCTGCAGTGACTGGGAAAACCCTGGCGACTAGTCTTGGACTCCTGTTGATAGATCCAGTAATGACCTCAGAACTCCATCTGGATTTGTTCAGAACGCTCGGTTGCCGCCGGGCGTTTTTTATTGGTGAGAATCCAGGGGTCCCCAATAATTACGATTTAAATCCTTCAAACTTCCCAAAGGCGAGCCCTAGTGACATTAGAAAACCGACTGTAAAAAGTACAGTCGGCATTATCTCATATTATAAAAGCCAGTCATTAGGCCTATCTGACAATTCCTGAATAGAGTTCATAAACAATCCTGCATGATAACCATCACAAACAGAATGATGTACCTGTAAAGATAGCGGTAAATATATTGAATTACCTTTATTAATGAATTTTCCTGCTGTAATAATGGGTAGAAGGTAATTACTATTATTATTGATATTTAAGTTAAACCCAGTAAATGAAGTCCATGGAATAATAGAAAGAGAAAAAGCATTTTCAGGTATAGGTGTTTTGGGAAACAATTTCCCCGAACCATTATATTTCTCTACATCAGAAAGGTATAAATCATAAAACTCTTTGAAGTCATTCTTTACAGGAGTCCAAATACCAGAGAATGTTTTAGATACACCATCAAAAATTGTATAAAGTGGCTCTAACTTATCCCAATAACCTAACTCTCCGTCGCTATTGTAACCAGTTCTAAAAGCTGTATTTGAGTTTATCACCCTTGTCACTAAGAAAATAAATGCAGGGTAAAATTTATATCCTTCTTGTTTTATGTTTCGGTATAAAACACTAATATCAATTTCTGTGGTTATACTAAAAGTCGTTTGTTGGTTCAAATAATGATTAAATATCTCTTTTCTCTTCCAATTGTCTAAATCAATTTTATTAAAGTTCATTTGATATGCCTCCTAAATTTTTATCTAAAGTGAATTTAGGAGGCTTACTTGTCTGCTTTCTTCATTAGAATCAATCCTTTTTTAAAAGTCAATCCCGTTTGTTGAAGACTTTTGTCCTTTTCCGCTGCATAAACAATATGGCCCGTTTGTTGAACTACTCTTTAATAAAATAATTTTTCCGTTCCCAATTCCACATTGCAATAATAGAAAATCCATCTTCATCGGCTTTTTCGTCATCATCTGTATGAATCAAATCGCCTTCTTCTGTGTCATCAAGGTTTAATTTTTTATGTATTTCTTTTAACAAACCACCATAGGAGATTAACCTTTTACGGTGTAAACCTTCCTCCAAATCAGACAAACGTTTCAAATTCTTTTCTTCATCATCGGTCATAAAATCCGTATCCTTTACAGGATATTTTGCAGTTTCGTCAATTGCCGATTGTATATCCGATTTATATTTATTTTTCGGTCGAATCATTTGAACTTTTACATTTGGATCATAGTCTAATTTCATTGCCTTTTTCCAAAATTGAATCCATTGTTTTTGATTCACGTAGTTTTCTGTATTCTTAAAATAAGTTGGTTCCACACATACCAATACATGCATGTGCTGATTATAAGAATTATCTTTATTATTTATTGTCACTTCCGTTGCACGCATAAAACCAACAAGATTTTTATTAATTTTTTTATATTGCATCATTCGGCGAAATCCTTGAGCCATATCTGACAAACTCTTATTTAATTCTTCGCCATCATAAACATTTTTAACTGTTAATGTGAGAAACAACCAACGAACTGTTGGCTTTTGTTTAATAACTTCAGCAACAACCTTTTGTGACTGAATGCCATGTTTCATTGCTCTCCTCCAGTTGCACATTGGACAAAGCCTGGATTTACAAAACCACACTCGATACAACTTTCTTTCGCCTGTTTCACGATTTTGTTTATACTCTAATATTTCAGCACAATCTTTTACTCTTTCAGCCTTTTTAAATTCAAGAATATGCAGAAGTTCAAAGTAATCAACATTAGCGATTTTCTTTTCTCTCCATGGTCTCACTTTTCCACTTTTTGTCTTGTCCACTAAAACCCTTGATTTTTCATCTGAATAAATGCTACTATTAGGACACATAATATTAAAAGAAACCCCCATCTATTTAGTTATTTGTTTGGTCACTTATAACTTTAACAGATGGGGTTTTTCTGTGCAACCAATTTTAAGGGTTTTCCAATACTTTAAAACACATACATACCAACACTTCAACGCACCTTTCAGCAACTAAAATAAAAATGACGTTATTTCTATATGTATCAAGATAAGAAAGAACAAGTTCAAAACCATCAAAAAAAGACACCTTTTCAGGTGCTTTTTTTATTTTATAAACTCATTCCCTGATCTCGACTTCGTTCTTTTTTTACCTCTCGGTTATGAGTTAGTTCAAATTCGTTCTTTTTAGGTTCTAAATCGTGTTTTTCTTGGAATTGTGCTGTTTTATCCTTTACCTTGTCTACAAACCCCTTAAAAACGTTTTTAAAGGCTTTTAAGCGTCTGTACGTTCCTTAAGGAATTATTCCTTAGTGCTTTCTAGGTTAATGTCATGATAATAATGGTTTCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTCCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTGTTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGCAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCTTAATAAGATGATCTTCTTGAGATCGTTTTGGTCTGCGCGTAATCTCTTGCTCTGAAAACGAAAAAACCGCCTTGCAGGGAGGTTTTTCGAAGGTTCTCTGAGCTACCAACTCTTTGAACCGAGGTAACTGGCTTGCAGGAGCGCAGTCACCAAAACTTGTCCTTTCAGTTTAGCCTTAACCGGCGCATGACTTCAAGACTAACTCCTCTAAATCAATTACCAGTGGCTGCTGCCAGTGGTGCTTTTGCATGTCTTTCCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGACTGAACGGGGGGTTCGTGCATACAGTCCAGCTTGGAGCGAACTGCCTACCCGGAACTGAGTGTCAGGCGTGGAATGAGACAAACGCGGCCATAACAGCGGAATGACACCGGTAAACCGAAAGGCAGGAACAGGAGAGCGCACGAGGGAGCCGCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCACTGATTTGAGCGTCAGATTTCGTGATGCTTGTCAGGGGGCGGAGCCTATGGAAAAACGCTTTGCCCGAGCCTATGGAAAAACGCTTTGCCCCACACAGGCTCTTGAACAAGGGATAACAATTTGTCATAGCTGTATTCGTTACAAGGAGGATTTTCGAAAAAACACCCTAACGGGTGTTTTTTTATAGCTGGTCTCCCCAAGTGCTGTAAAAAACGCCGAATGAAGCGGATGAAATTGCTCATCGTCTCGTGAAAAAGCCGAAGAAGGTTAAGCCTGGGTATAAAAAGAAAATGAGCTATGAGATGGAGAAAGCCATAACCATGAGTGATAACACTGGTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTTTTTTTCTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCCTCAATGATC >pCas9g2 (SEQ ID No: 234)tccttatccggttaagatggCTTTTAAATCAATTTTCAGCTCCTGTATACAATTACCAAAGTTTTTCTGAATGAAGCCATGTGTTTTGACACATTCTATACTCACAAGGAGGTGAGACACatggataagaaatactcaataggctTAGATATCGGCACAAATAGCGTCGGATGGGCGGTGATCACTGATGAATATAAGGTTCCGTCTAAAAAGTTCAAGGTTCTGGGAAATACAGACCGCCACAGTATCAAAAAAAATCTTATAGGGGCTCTTTTATTTGACAGTGGAGAGACAGCGGAAGCGACTCGTCTCAAACGGACAGCTCGTAGAAGGTATACACGTCGGAAGAATCGTATTTGTTATCTACAGGAGATTTTTTCAAATGAGATGGCGAAAGTAGATGATAGTTTCTTTCATCGACTTGAAGAGTCTTTTTTGGTGGAAGAAGACAAGAAGCATGAACGTCATCCTATTTTTGGAAATATAGTAGATGAAGTTGCTTATCATGAGAAATATCCAACTATCTATCATCTGCGAAAAAAATTGGTAGATTCTACTGATAAAGCGGATTTGCGCTTAATCTATTTGGCCTTAGCGCATATGATTAAGTTTCGTGGTCATTTTTTGATTGAGGGAGATTTAAATCCTGATAATAGTGATGTGGACAAACTATTTATCCAGTTGGTACAAACCTACAATCAATTATTTGAAGAAAACCCTATTAACGCAAGTGGAGTAGATGCTAAAGCGATTCTTTCTGCACGATTGAGTAAATCAAGACGATTAGAAAATCTCATTGCTCAGCTCCCCGGTGAGAAGAAAAATGGCTTATTTGGGAATCTCATTGCTTTGTCATTGGGTTTGACCCCTAATTTTAAATCAAATTTTGATTTGGCAGAAGATGCTAAATTACAGCTTTCAAAAGATACTTACGATGATGATTTAGATAATTTATTGGCGCAAATTGGAGATCAATATGCTGATTTGTTTTTGGCAGCTAAGAATTTATCAGATGCTATTTTACTTTCAGATATCCTAAGAGTAAATACTGAAATAACTAAGGCTCCCCTATCAGCTTCAATGATTAAACGCTACGATGAACATCATCAAGACTTGACTCTTTTAAAAGCTTTAGTTCGACAACAACTTCCAGAAAAGTATAAAGAAATCTTTTTTGATCAATCAAAAAACGGATATGCAGGTTATATTGATGGGGGAGCTAGCCAAGAAGAATTTTATAAATTTATCAAACCAATTTTAGAAAAAATGGATGGTACTGAGGAATTATTGGTGAAACTAAATCGTGAAGATTTGCTGCGCAAGCAACGGACCTTTGACAACGGCTCTATTCCCCATCAAATTCACTTGGGTGAGCTGCATGCTATTTTGAGAAGACAAGAAGACTTTTATCCATTTTTAAAAGACAATCGTGAGAAGATTGAAAAAATCTTGACTTTTCGAATTCCTTATTATGTTGGTCCATTGGCGCGTGGCAATAGTCGTTTTGCATGGATGACTCGGAAGTCTGAAGAAACAATTACCCCATGGAATTTTGAAGAAGTTGTCGATAAAGGTGCTTCAGCTCAATCATTTATTGAACGCATGACAAACTTTGATAAAAATCTTCCAAATGAAAAAGTACTACCAAAACATAGTTTGCTTTATGAGTATTTTACGGTTTATAACGAATTGACAAAGGTCAAATATGTTACTGAAGGAATGCGAAAACCAGCATTTCTTTCAGGTGAACAGAAGAAAGCCATTGTTGATTTACTCTTCAAAACAAATCGAAAAGTAACCGTTAAGCAATTAAAAGAAGATTATTTCAAAAAAATAGAATGTTTTGATAGTGTTGAAATTTCAGGAGTTGAAGATAGATTTAATGCTTCATTAGGTACCTACCATGATTTGCTAAAAATTATTAAAGATAAAGATTTTTTGGATAATGAAGAAAATGAAGATATCTTAGAGGATATTGTTTTAACATTGACCTTATTTGAAGATAGGGAGATGATTGAGGAAAGACTTAAAACATATGCTCACCTCTTTGATGATAAGGTGATGAAACAGCTTAAACGTCGCCGTTATACTGGTTGGGGACGTTTGTCTCGAAAATTGATTAATGGTATTAGGGATAAGCAATCTGGCAAAACAATATTAGATTTTTTGAAATCAGATGGTTTTGCCAATCGCAATTTTATGCAGCTGATCCATGATGATAGTTTGACATTTAAAGAAGACATTCAAAAAGCACAAGTGTCTGGACAAGGCGATAGTTTACATGAACATATTGCAAATTTAGCTGGTAGCCCTGCTATTAAAAAAGGTATTTTACAGACTGTAAAAGTTGTTGATGAATTGGTCAAAGTAATGGGGCGGCATAAGCCAGAAAATATCGTTATTGAAATGGCACGTGAAAATCAGACAACTCAAAAGGGCCAGAAAAATTCGCGAGAGCGTATGAAACGAATCGAAGAAGGTATCAAAGAATTAGGAAGTCAGATTCTTAAAGAGCATCCTGTTGAAAATACTCAATTGCAAAATGAAAAGCTCTATCTCTATTATCTCCAAAATGGAAGAGACATGTATGTGGACCAAGAATTAGATATTAATCGTTTAAGTGATTATGATGTCGATCACATTGTTCCACAAAGTTTCCTTAAAGACGATTCAATAGACAATAAGGTCTTAACGCGTTCTGATAAAAATCGTGGTAAATCGGATAACGTTCCAAGTGAAGAAGTAGTCAAAAAGATGAAAAACTATTGGAGACAACTTCTAAACGCCAAGTTAATCACTCAACGTAAGTTTGATAATTTAACGAAAGCTGAACGTGGAGGTTTGAGTGAACTTGATAAAGCTGGTTTTATCAAACGCCAATTGGTTGAAACTCGCCAAATCACTAAGCATGTGGCACAAATTTTGGATAGTCGCATGAATACTAAATACGATGAAAATGATAAACTTATTCGAGAGGTTAAAGTGATTACCTTAAAATCTAAATTAGTTTCTGACTTCCGAAAAGATTTCCAATTCTATAAAGTACGTGAGATTAACAATTACCATCATGCCCATGATGCGTATCTAAATGCCGTCGTTGGAACTGCTTTGATTAAGAAATATCCAAAACTTGAATCGGAGTTTGTCTATGGTGATTATAAAGTTTATGATGTTCGTAAAATGATTGCTAAGTCTGAGCAAGAAATAGGCAAAGCAACCGCAAAATATTTCTTTTACTCTAATATCATGAACTTCTTCAAAACAGAAATTACACTTGCAAATGGAGAGATTCGCAAACGCCCTCTAATCGAAACTAATGGGGAAACTGGAGAAATTGTCTGGGATAAAGGGCGAGATTTTGCCACAGTGCGCAAAGTATTGTCCATGCCCCAAGTCAATATTGTCAAGAAAACAGAAGTACAGACAGGCGGATTCTCCAAGGAGTCAATTTTACCAAAAAGAAATTCGGACAAGCTTATTGCTCGTAAAAAAGACTGGGATCCAAAAAAATATGGTGGTTTTGATAGTCCAACGGTAGCTTATTCAGTCCTAGTGGTTGCTAAGGTGGAAAAAGGGAAATCGAAGAAGTTAAAATCCGTTAAAGAGTTACTAGGGATCACAATTATGGAAAGAAGTTCCTTTGAAAAAAATCCGATTGACTTTTTAGAAGCTAAAGGATATAAGGAAGTTAAAAAAGACTTAATCATTAAACTACCTAAATATAGTCTTTTTGAGTTAGAAAACGGTCGTAAACGGATGCTGGCTAGTGCCGGAGAATTACAAAAAGGAAATGAGCTGGCTCTGCCAAGCAAATATGTGAATTTTTTATATTTAGCTAGTCATTATGAAAAGTTGAAGGGTAGTCCAGAAGATAACGAACAAAAACAATTGTTTGTGGAGCAGCATAAGCATTATTTAGATGAGATTATTGAGCAAATCAGTGAATTTTCTAAGCGTGTTATTTTAGCAGATGCCAATTTAGATAAAGTTCTTAGTGCATATAACAAACATAGAGACAAACCAATACGTGAACAAGCAGAAAATATTATTCATTTATTTACGTTGACGAATCTTGGAGCTCCCGCTGCTTTTAAATATTTTGATACAACAATTGATCGTAAACGATATACGTCTACAAAAGAAGTTTTAGATGCCACTCTTATCCATCAATCCATCACTGGTCTTTATGAAACACGCATTGATTTGAGTCAGCTAGGAGGTGACTGATAATCAAATGTCAGACGAAAATGCCAATTATTGAAGCGGCTAACGCCGCTTTTTTTGTTTCTGGTCTCCCTTGCTTGTACTTTACAGTATAGCTTCTAGAGATCTGCAGTGACTGGAGCTTCTAGAGATCAGGTCAGACGCGATTTCCTGGGTGCTCGAGCCATGGGAAAGCGGTGGTGGAAAAAACGCCGAATGAAGCGGATGAAATTGCTCATCGTCTCGTGAAAAAGCCGAAGAAGGTTAAGCCTGGGTATAAAAAGAAAATGAGCTATGAGATGGAGAAATTGAAGTCATGCGCCGGTTAGTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTTTTTTTCTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCCTCAATGATCCGACAGGAAGTGGTATTAGCGACTCCTACAAGGAATAGGTGTCTGGGTCATGCAGTGACTGGGAAAACCCTGGCGACTAGTCTTGGACTCCTGTTGATAGATCCAGTAATGACCTCAGAACTCCATCTGGATTTGTTCAGAACGCTCGGTTGCCGCCGGGCGTTTTTTATTGGTGAGAATCCAGGGGTCCCCAATAATTACGATTTAAATCCTTCAAACTTCCCAAAGGCGAGCCCTAGTGACATTAGAAAACCGACTGTAAAAAGTACAGTCGGCATTATCTCATATTATAAAAGCCAGTCATTAGGCCTATCTGACAATTCCTGAATAGAGTTCATAAACAATCCTGCATGATAACCATCACAAACAGAATGATGTACCTGTAAAGATAGCGGTAAATATATTGAATTACCTTTATTAATGAATTTTCCTGCTGTAATAATGGGTAGAAGGTAATTACTATTATTATTGATATTTAAGTTAAACCCAGTAAATGAAGTCCATGGAATAATAGAAAGAGAAAAAGCATTTTCAGGTATAGGTGTTTTGGGAAACAATTTCCCCGAACCATTATATTTCTCTACATCAGAAAGGTATAAATCATAAAACTCTTTGAAGTCATTCTTTACAGGAGTCCAAATACCAGAGAATGTTTTAGATACACCATCAAAAATTGTATAAAGTGGCTCTAACTTATCCCAATAACCTAACTCTCCGTCGCTATTGTAACCAGTTCTAAAAGCTGTATTTGAGTTTATCACCCTTGTCACTAAGAAAATAAATGCAGGGTAAAATTTATATCCTTCTTGTTTTATGTTTCGGTATAAAACACTAATATCAATTTCTGTGGTTATACTAAAAGTCGTTTGTTGGTTCAAATAATGATTAAATATCTCTTTTCTCTTCCAATTGTCTAAATCAATTTTATTAAAGTTCATTTGATATGCCTCCTAAATTTTTATCTAAAGTGAATTTAGGAGGCTTACTTGTCTGCTTTCTTCATTAGAATCAATCCTTTTTTAAAAGTCAATCCCGTTTGTTGAAGACTTTTGTCCTTTTCCGCTGCATAAACAATATGGCCCGTTTGTTGAACTACTCTTTAATAAAATAATTTTTCCGTTCCCAATTCCACATTGCAATAATAGAAAATCCATCTTCATCGGCTTTTTCGTCATCATCTGTATGAATCAAATCGCCTTCTTCTGTGTCATCAAGGTTTAATTTTTTATGTATTTCTTTTAACAAACCACCATAGGAGATTAACCTTTTACGGTGTAAACCTTCCTCCAAATCAGACAAACGTTTCAAATTCTTTTCTTCATCATCGGTCATAAAATCCGTATCCTTTACAGGATATTTTGCAGTTTCGTCAATTGCCGATTGTATATCCGATTTATATTTATTTTTCGGTCGAATCATTTGAACTTTTACATTTGGATCATAGTCTAATTTCATTGCCTTTTTCCAAAATTGAATCCATTGTTTTTGATTCACGTAGTTTTCTGTATTCTTAAAATAAGTTGGTTCCACACATACCAATACATGCATGTGCTGATTATAAGAATTATCTTTATTATTTATTGTCACTTCCGTTGCACGCATAAAACCAACAAGATTTTTATTAATTTTTTTATATTGCATCATTCGGCGAAATCCTTGAGCCATATCTGACAAACTCTTATTTAATTCTTCGCCATCATAAACATTTTTAACTGTTAATGTGAGAAACAACCAACGAACTGTTGGCTTTTGTTTAATAACTTCAGCAACAACCTTTTGTGACTGAATGCCATGTTTCATTGCTCTCCTCCAGTTGCACATTGGACAAAGCCTGGATTTACAAAACCACACTCGATACAACTTTCTTTCGCCTGTTTCACGATTTTGTTTATACTCTAATATTTCAGCACAATCTTTTACTCTTTCAGCCTTTTTAAATTCAAGAATATGCAGAAGTTCAAAGTAATCAACATTAGCGATTTTCTTTTCTCTCCATGGTCTCACTTTTCCACTTTTTGTCTTGTCCACTAAAACCCTTGATTTTTCATCTGAATAAATGCTACTATTAGGACACATAATATTAAAAGAAACCCCCATCTATTTAGTTATTTGTTTGGTCACTTATAACTTTAACAGATGGGGTTTTTCTGTGCAACCAATTTTAAGGGTTTTCCAATACTTTAAAACACATACATACCAACACTTCAACGCACCTTTCAGCAACTAAAATAAAAATGACGTTATTTCTATATGTATCAAGATAAGAAAGAACAAGTTCAAAACCATCAAAAAAAGACACCTTTTCAGGTGCTTTTTTTATTTTATAAACTCATTCCCTGATCTCGACTTCGTTCTTTTTTTACCTCTCGGTTATGAGTTAGTTCAAATTCGTTCTTTTTAGGTTCTAAATCGTGTTTTTCTTGGAATTGTGCTGTTTTATCCTTTACCTTGTCTACAAACCCCTTAAAAACGTTTTTAAAGGCTTTTAAGCGTCTGTACGTTCCTTAAGGAATTATTCCTTAGTGCTTTCTAGGTTAATGTCATGATAATAATGGTTTCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTCCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTGTTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGCAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCTTAATAAGATGATCTTCTTGAGATCGTTTTGGTCTGCGCGTAATCTCTTGCTCTGAAAACGAAAAAACCGCCTTGCAGGGAGGTTTTTCGAAGGTTCTCTGAGCTACCAACTCTTTGAACCGAGGTAACTGGCTTGCAGGAGCGCAGTCACCAAAACTTGTCCTTTCAGTTTAGCCTTAACCGGCGCATGACTTCAAGACTAACTCCTCTAAATCAATTACCAGTGGCTGCTGCCAGTGGTGCTTTTGCATGTCTTTCCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGACTGAACGGGGGGTTCGTGCATACAGTCCAGCTTGGAGCGAACTGCCTACCCGGAACTGAGTGTCAGGCGTGGAATGAGACAAACGCGGCCATAACAGCGGAATGACACCGGTAAACCGAAAGGCAGGAACAGGAGAGCGCACGAGGGAGCCGCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCACTGATTTGAGCGTCAGATTTCGTGATGCTTGTCAGGGGGCGGAGCCTATGGAAAAACGCTTTGCCCGAGCCTATGGAAAAACGCTTTGCCCCACACAGGCTCTTGAACAAGGGATAACAATTTGTCATAGCTGTATTCGTTACAAGGAGGATTTTCGAAAAAACACCCTAACGGGTGTTTTTTTATAGCTGGTCTCCCCAAGTGCTGTAAAAAACGCCGAATGAAGCGGATGAAATTGCTCATCGTCTCGTGAAAAAGCCGAAGAAGGTTAAGCCTGGGTATAAAAAGAAAATGAGCTATGAGATGGAGAAAGCCATAACCATGAGTGATAACACTGGTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTTTTTTTCTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCCTCAATGATC >pCas9g1-D15 (SEQ ID No: 235)tccttatccggttaagatggCTTTTAAATCAATTTTCAGCTCCTGTATACAATTACCAAAGTTTTTCTGAATGAAGCCATGTGTTTTGACACATTCTATACTCACAAGGAGGTGAGACACatgagtaaatcctggggcaaATTCATCGAGGAGGAAGAGGCGGAAATGGCTTCCCGTCGTAATCTAATGATTGTCGATGGAACTAACTTAGGCTTTCGCTTCAAACATAACAATAGTAAAAAACCATTTGCCTCAAGTTATGTTTCAACTATTCAATCTCTGGCAAAATCCTACTCTGCCAGAACTACGATTGTTCTAGGTGATAAGGGCAAAAGCGTGTTCAGACTAGAACATCTACCAGAGTATAAAGGTAATCGTGATGAAAAGTACGCACAACGTACGGAAGAGGAGAAAGCGCTAGATGAGCAGTTCTTCGAATACCTCAAAGATGCTTTCGAGTTGTGTAAAACTACATTCCCAACTTTTACCATTCGTGGTGTAGAAGCAGATGACATGGCGGCGTATATTGTTAAGCTCATCGGGCATCTTTATGATCACGTTTGGCTAATATCTACAGATGGTGACTGGGATACTTTATTAACGGATAAAGTTTCTCGTTTTTCTTTCACAACACGTCGTGAGTATCATCTTCGTGATATGTATGAGCACCATAACGTGGACGACGTAGAACAGTTTATCTCCCTGAAAGCAATTATGGGAGATCTAGGAGATAATATTCGTGGTGTTGAAGGAATAGGAGCAAAACGCGGATATAATATTATTCGTGAGTTTGGTAACGTACTGGATATTATTGATCAGCTTCCACTGCCTGGAAAGCAGAAATATATACAGAACCTGAATGCATCGGAAGAACTGCTTTTCCGAAACTTGATTCTGGTTGATTTACCTACCTACTGTGTGGATGCTATTGCTGCTGTAGGTCAAGATGTGTTAGATAAGTTCACGAAAGACATCCTTGAGATCGCGGAACAATGATAAGCTCTTAAAGGGGGTTTTAGATACCAGAGATGGATAAGAAATACTCAATAGGCTTAGATATCGGCACAAATAGCGTCGGATGGGCGGTGATCACTGATGAATATAAGGTTCCGTCTAAAAAGTTCAAGGTTCTGGGAAATACAGACCGCCACAGTATCAAAAAAAATCTTATAGGGGCTCTTTTATTTGACAGTGGAGAGACAGCGGAAGCGACTCGTCTCAAACGGACAGCTCGTAGAAGGTATACACGTCGGAAGAATCGTATTTGTTATCTACAGGAGATTTTTTCAAATGAGATGGCGAAAGTAGATGATAGTTTCTTTCATCGACTTGAAGAGTCTTTTTTGGTGGAAGAAGACAAGAAGCATGAACGTCATCCTATTTTTGGAAATATAGTAGATGAAGTTGCTTATCATGAGAAATATCCAACTATCTATCATCTGCGAAAAAAATTGGTAGATTCTACTGATAAAGCGGATTTGCGCTTAATCTATTTGGCCTTAGCGCATATGATTAAGTTTCGTGGTCATTTTTTGATTGAGGGAGATTTAAATCCTGATAATAGTGATGTGGACAAACTATTTATCCAGTTGGTACAAACCTACAATCAATTATTTGAAGAAAACCCTATTAACGCAAGTGGAGTAGATGCTAAAGCGATTCTTTCTGCACGATTGAGTAAATCAAGACGATTAGAAAATCTCATTGCTCAGCTCCCCGGTGAGAAGAAAAATGGCTTATTTGGGAATCTCATTGCTTTGTCATTGGGTTTGACCCCTAATTTTAAATCAAATTTTGATTTGGCAGAAGATGCTAAATTACAGCTTTCAAAAGATACTTACGATGATGATTTAGATAATTTATTGGCGCAAATTGGAGATCAATATGCTGATTTGTTTTTGGCAGCTAAGAATTTATCAGATGCTATTTTACTTTCAGATATCCTAAGAGTAAATACTGAAATAACTAAGGCTCCCCTATCAGCTTCAATGATTAAACGCTACGATGAACATCATCAAGACTTGACTCTTTTAAAAGCTTTAGTTCGACAACAACTTCCAGAAAAGTATAAAGAAATCTTTTTTGATCAATCAAAAAACGGATATGCAGGTTATATTGATGGGGGAGCTAGCCAAGAAGAATTTTATAAATTTATCAAACCAATTTTAGAAAAAATGGATGGTACTGAGGAATTATTGGTGAAACTAAATCGTGAAGATTTGCTGCGCAAGCAACGGACCTTTGACAACGGCTCTATTCCCCATCAAATTCACTTGGGTGAGCTGCATGCTATTTTGAGAAGACAAGAAGACTTTTATCCATTTTTAAAAGACAATCGTGAGAAGATTGAAAAAATCTTGACTTTTCGAATTCCTTATTATGTTGGTCCATTGGCGCGTGGCAATAGTCGTTTTGCATGGATGACTCGGAAGTCTGAAGAAACAATTACCCCATGGAATTTTGAAGAAGTTGTCGATAAAGGTGCTTCAGCTCAATCATTTATTGAACGCATGACAAACTTTGATAAAAATCTTCCAAATGAAAAAGTACTACCAAAACATAGTTTGCTTTATGAGTATTTTACGGTTTATAACGAATTGACAAAGGTCAAATATGTTACTGAAGGAATGCGAAAACCAGCATTTCTTTCAGGTGAACAGAAGAAAGCCATTGTTGATTTACTCTTCAAAACAAATCGAAAAGTAACCGTTAAGCAATTAAAAGAAGATTATTTCAAAAAAATAGAATGTTTTGATAGTGTTGAAATTTCAGGAGTTGAAGATAGATTTAATGCTTCATTAGGTACCTACCATGATTTGCTAAAAATTATTAAAGATAAAGATTTTTTGGATAATGAAGAAAATGAAGATATCTTAGAGGATATTGTTTTAACATTGACCTTATTTGAAGATAGGGAGATGATTGAGGAAAGACTTAAAACATATGCTCACCTCTTTGATGATAAGGTGATGAAACAGCTTAAACGTCGCCGTTATACTGGTTGGGGACGTTTGTCTCGAAAATTGATTAATGGTATTAGGGATAAGCAATCTGGCAAAACAATATTAGATTTTTTGAAATCAGATGGTTTTGCCAATCGCAATTTTATGCAGCTGATCCATGATGATAGTTTGACATTTAAAGAAGACATTCAAAAAGCACAAGTGTCTGGACAAGGCGATAGTTTACATGAACATATTGCAAATTTAGCTGGTAGCCCTGCTATTAAAAAAGGTATTTTACAGACTGTAAAAGTTGTTGATGAATTGGTCAAAGTAATGGGGCGGCATAAGCCAGAAAATATCGTTATTGAAATGGCACGTGAAAATCAGACAACTCAAAAGGGCCAGAAAAATTCGCGAGAGCGTATGAAACGAATCGAAGAAGGTATCAAAGAATTAGGAAGTCAGATTCTTAAAGAGCATCCTGTTGAAAATACTCAATTGCAAAATGAAAAGCTCTATCTCTATTATCTCCAAAATGGAAGAGACATGTATGTGGACCAAGAATTAGATATTAATCGTTTAAGTGATTATGATGTCGATCACATTGTTCCACAAAGTTTCCTTAAAGACGATTCAATAGACAATAAGGTCTTAACGCGTTCTGATAAAAATCGTGGTAAATCGGATAACGTTCCAAGTGAAGAAGTAGTCAAAAAGATGAAAAACTATTGGAGACAACTTCTAAACGCCAAGTTAATCACTCAACGTAAGTTTGATAATTTAACGAAAGCTGAACGTGGAGGTTTGAGTGAACTTGATAAAGCTGGTTTTATCAAACGCCAATTGGTTGAAACTCGCCAAATCACTAAGCATGTGGCACAAATTTTGGATAGTCGCATGAATACTAAATACGATGAAAATGATAAACTTATTCGAGAGGTTAAAGTGATTACCTTAAAATCTAAATTAGTTTCTGACTTCCGAAAAGATTTCCAATTCTATAAAGTACGTGAGATTAACAATTACCATCATGCCCATGATGCGTATCTAAATGCCGTCGTTGGAACTGCTTTGATTAAGAAATATCCAAAACTTGAATCGGAGTTTGTCTATGGTGATTATAAAGTTTATGATGTTCGTAAAATGATTGCTAAGTCTGAGCAAGAAATAGGCAAAGCAACCGCAAAATATTTCTTTTACTCTAATATCATGAACTTCTTCAAAACAGAAATTACACTTGCAAATGGAGAGATTCGCAAACGCCCTCTAATCGAAACTAATGGGGAAACTGGAGAAATTGTCTGGGATAAAGGGCGAGATTTTGCCACAGTGCGCAAAGTATTGTCCATGCCCCAAGTCAATATTGTCAAGAAAACAGAAGTACAGACAGGCGGATTCTCCAAGGAGTCAATTTTACCAAAAAGAAATTCGGACAAGCTTATTGCTCGTAAAAAAGACTGGGATCCAAAAAAATATGGTGGTTTTGATAGTCCAACGGTAGCTTATTCAGTCCTAGTGGTTGCTAAGGTGGAAAAAGGGAAATCGAAGAAGTTAAAATCCGTTAAAGAGTTACTAGGGATCACAATTATGGAAAGAAGTTCCTTTGAAAAAAATCCGATTGACTTTTTAGAAGCTAAAGGATATAAGGAAGTTAAAAAAGACTTAATCATTAAACTACCTAAATATAGTCTTTTTGAGTTAGAAAACGGTCGTAAACGGATGCTGGCTAGTGCCGGAGAATTACAAAAAGGAAATGAGCTGGCTCTGCCAAGCAAATATGTGAATTTTTTATATTTAGCTAGTCATTATGAAAAGTTGAAGGGTAGTCCAGAAGATAACGAACAAAAACAATTGTTTGTGGAGCAGCATAAGCATTATTTAGATGAGATTATTGAGCAAATCAGTGAATTTTCTAAGCGTGTTATTTTAGCAGATGCCAATTTAGATAAAGTTCTTAGTGCATATAACAAACATAGAGACAAACCAATACGTGAACAAGCAGAAAATATTATTCATTTATTTACGTTGACGAATCTTGGAGCTCCCGCTGCTTTTAAATATTTTGATACAACAATTGATCGTAAACGATATACGTCTACAAAAGAAGTTTTAGATGCCACTCTTATCCATCAATCCATCACTGGTCTTTATGAAACACGCATTGATTTGAGTCAGCTAGGAGGTGACTGATAATCAAATGTCAGACGAAAATGCCAATTATTGAAGCGGCTAACGCCGCTTTTTTTGTTTCTGGTCTCCCTTGCTTGTACTTTACAGTATAGCTTCTAGAGATCTGCAGTGACTGGAGCTTCTAGAGATCTGCAGTGACTGGGAAAACCCTGGCGACTAGTCTTGGACTCCTGTTGATAGATCCAGTAATGACCTCAGAACTCCATCTGGATTTGTTCAGAACGCTCGGTTGCCGCCGGGCGTTTTTTATTGGTGAGAATCCAGGGGTCCCCAATAATTACGATTTAAATCCTTCAAACTTCCCAAAGGCGAGCCCTAGTGACATTAGAAAACCGACTGTAAAAAGTACAGTCGGCATTATCTCATATTATAAAAGCCAGTCATTAGGCCTATCTGACAATTCCTGAATAGAGTTCATAAACAATCCTGCATGATAACCATCACAAACAGAATGATGTACCTGTAAAGATAGCGGTAAATATATTGAATTACCTTTATTAATGAATTTTCCTGCTGTAATAATGGGTAGAAGGTAATTACTATTATTATTGATATTTAAGTTAAACCCAGTAAATGAAGTCCATGGAATAATAGAAAGAGAAAAAGCATTTTCAGGTATAGGTGTTTTGGGAAACAATTTCCCCGAACCATTATATTTCTCTACATCAGAAAGGTATAAATCATAAAACTCTTTGAAGTCATTCTTTACAGGAGTCCAAATACCAGAGAATGTTTTAGATACACCATCAAAAATTGTATAAAGTGGCTCTAACTTATCCCAATAACCTAACTCTCCGTCGCTATTGTAACCAGTTCTAAAAGCTGTATTTGAGTTTATCACCCTTGTCACTAAGAAAATAAATGCAGGGTAAAATTTATATCCTTCTTGTTTTATGTTTCGGTATAAAACACTAATATCAATTTCTGTGGTTATACTAAAAGTCGTTTGTTGGTTCAAATAATGATTAAATATCTCTTTTCTCTTCCAATTGTCTAAATCAATTTTATTAAAGTTCATTTGATATGCCTCCTAAATTTTTATCTAAAGTGAATTTAGGAGGCTTACTTGTCTGCTTTCTTCATTAGAATCAATCCTTTTTTAAAAGTCAATCCCGTTTGTTGAAGACTTTTGTCCTTTTCCGCTGCATAAACAATATGGCCCGTTTGTTGAACTACTCTTTAATAAAATAATTTTTCCGTTCCCAATTCCACATTGCAATAATAGAAAATCCATCTTCATCGGCTTTTTCGTCATCATCTGTATGAATCAAATCGCCTTCTTCTGTGTCATCAAGGTTTAATTTTTTATGTATTTCTTTTAACAAACCACCATAGGAGATTAACCTTTTACGGTGTAAACCTTCCTCCAAATCAGACAAACGTTTCAAATTCTTTTCTTCATCATCGGTCATAAAATCCGTATCCTTTACAGGATATTTTGCAGTTTCGTCAATTGCCGATTGTATATCCGATTTATATTTATTTTTCGGTCGAATCATTTGAACTTTTACATTTGGATCATAGTCTAATTTCATTGCCTTTTTCCAAAATTGAATCCATTGTTTTTGATTCACGTAGTTTTCTGTATTCTTAAAATAAGTTGGTTCCACACATACCAATACATGCATGTGCTGATTATAAGAATTATCTTTATTATTTATTGTCACTTCCGTTGCACGCATAAAACCAACAAGATTTTTATTAATTTTTTTATATTGCATCATTCGGCGAAATCCTTGAGCCATATCTGACAAACTCTTATTTAATTCTTCGCCATCATAAACATTTTTAACTGTTAATGTGAGAAACAACCAACGAACTGTTGGCTTTTGTTTAATAACTTCAGCAACAACCTTTTGTGACTGAATGCCATGTTTCATTGCTCTCCTCCAGTTGCACATTGGACAAAGCCTGGATTTACAAAACCACACTCGATACAACTTTCTTTCGCCTGTTTCACGATTTTGTTTATACTCTAATATTTCAGCACAATCTTTTACTCTTTCAGCCTTTTTAAATTCAAGAATATGCAGAAGTTCAAAGTAATCAACATTAGCGATTTTCTTTTCTCTCCATGGTCTCACTTTTCCACTTTTTGTCTTGTCCACTAAAACCCTTGATTTTTCATCTGAATAAATGCTACTATTAGGACACATAATATTAAAAGAAACCCCCATCTATTTAGTTATTTGTTTGGTCACTTATAACTTTAACAGATGGGGTTTTTCTGTGCAACCAATTTTAAGGGTTTTCCAATACTTTAAAACACATACATACCAACACTTCAACGCACCTTTCAGCAACTAAAATAAAAATGACGTTATTTCTATATGTATCAAGATAAGAAAGAACAAGTTCAAAACCATCAAAAAAAGACACCTTTTCAGGTGCTTTTTTTATTTTATAAACTCATTCCCTGATCTCGACTTCGTTCTTTTTTTACCTCTCGGTTATGAGTTAGTTCAAATTCGTTCTTTTTAGGTTCTAAATCGTGTTTTTCTTGGAATTGTGCTGTTTTATCCTTTACCTTGTCTACAAACCCCTTAAAAACGTTTTTAAAGGCTTTTAAGCGTCTGTACGTTCCTTAAGGAATTATTCCTTAGTGCTTTCTAGGTTAATGTCATGATAATAATGGTTTCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTCCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTGTTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGCAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCTTAATAAGATGATCTTCTTGAGATCGTTTTGGTCTGCGCGTAATCTCTTGCTCTGAAAACGAAAAAACCGCCTTGCAGGGAGGTTTTTCGAAGGTTCTCTGAGCTACCAACTCTTTGAACCGAGGTAACTGGCTTGCAGGAGCGCAGTCACCAAAACTTGTCCTTTCAGTTTAGCCTTAACCGGCGCATGACTTCAAGACTAACTCCTCTAAATCAATTACCAGTGGCTGCTGCCAGTGGTGCTTTTGCATGTCTTTCCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGACTGAACGGGGGGTTCGTGCATACAGTCCAGCTTGGAGCGAACTGCCTACCCGGAACTGAGTGTCAGGCGTGGAATGAGACAAACGCGGCCATAACAGCGGAATGACACCGGTAAACCGAAAGGCAGGAACAGGAGAGCGCACGAGGGAGCCGCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCACTGATTTGAGCGTCAGATTTCGTGATGCTTGTCAGGGGGCGGAGCCTATGGAAAAACGCTTTGCCCGAGCCTATGGAAAAACGCTTTGCCCCACACAGGCTCTTGAACAAGGGATAACAATTTGTCATAGCTGTATTCGTTACAAGGAGGATTTTCGAAAAAACACCCTAACGGGTGTTTTTTTATAGCTGGTCTCCCCAAGTGCTGTAAAAAACGCCGAATGAAGCGGATGAAATTGCTCATCGTCTCGTGAAAAAGCCGAAGAAGGTTAAGCCTGGGTATAAAAAGAAAATGAGCTATGAGATGGAGAAAGCCATAACCATGAGTGATAACACTGGTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTTTTTTTCTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCCTCAATGATC >pCas9g2-D15 (SEQ ID No: 236)tccttatccggttaagatggCTTTTAAATCAATTTTCAGCTCCTGTATACAATTACCAAAGTTTTTCTGAATGAAGCCATGTGTTTTGACACATTCTATACTCACAAGGAGGTGAGACACatgagtaaatcctggggcaaATTCATCGAGGAGGAAGAGGCGGAAATGGCTTCCCGTCGTAATCTAATGATTGTCGATGGAACTAACTTAGGCTTTCGCTTCAAACATAACAATAGTAAAAAACCATTTGCCTCAAGTTATGTTTCAACTATTCAATCTCTGGCAAAATCCTACTCTGCCAGAACTACGATTGTTCTAGGTGATAAGGGCAAAAGCGTGTTCAGACTAGAACATCTACCAGAGTATAAAGGTAATCGTGATGAAAAGTACGCACAACGTACGGAAGAGGAGAAAGCGCTAGATGAGCAGTTCTTCGAATACCTCAAAGATGCTTTCGAGTTGTGTAAAACTACATTCCCAACTTTTACCATTCGTGGTGTAGAAGCAGATGACATGGCGGCGTATATTGTTAAGCTCATCGGGCATCTTTATGATCACGTTTGGCTAATATCTACAGATGGTGACTGGGATACTTTATTAACGGATAAAGTTTCTCGTTTTTCTTTCACAACACGTCGTGAGTATCATCTTCGTGATATGTATGAGCACCATAACGTGGACGACGTAGAACAGTTTATCTCCCTGAAAGCAATTATGGGAGATCTAGGAGATAATATTCGTGGTGTTGAAGGAATAGGAGCAAAACGCGGATATAATATTATTCGTGAGTTTGGTAACGTACTGGATATTATTGATCAGCTTCCACTGCCTGGAAAGCAGAAATATATACAGAACCTGAATGCATCGGAAGAACTGCTTTTCCGAAACTTGATTCTGGTTGATTTACCTACCTACTGTGTGGATGCTATTGCTGCTGTAGGTCAAGATGTGTTAGATAAGTTCACGAAAGACATCCTTGAGATCGCGGAACAATGATAAGCTCTTAAAGGGGGTTTTAGATACCAGAGATGGATAAGAAATACTCAATAGGCTTAGATATCGGCACAAATAGCGTCGGATGGGCGGTGATCACTGATGAATATAAGGTTCCGTCTAAAAAGTTCAAGGTTCTGGGAAATACAGACCGCCACAGTATCAAAAAAAATCTTATAGGGGCTCTTTTATTTGACAGTGGAGAGACAGCGGAAGCGACTCGTCTCAAACGGACAGCTCGTAGAAGGTATACACGTCGGAAGAATCGTATTTGTTATCTACAGGAGATTTTTTCAAATGAGATGGCGAAAGTAGATGATAGTTTCTTTCATCGACTTGAAGAGTCTTTTTTGGTGGAAGAAGACAAGAAGCATGAACGTCATCCTATTTTTGGAAATATAGTAGATGAAGTTGCTTATCATGAGAAATATCCAACTATCTATCATCTGCGAAAAAAATTGGTAGATTCTACTGATAAAGCGGATTTGCGCTTAATCTATTTGGCCTTAGCGCATATGATTAAGTTTCGTGGTCATTTTTTGATTGAGGGAGATTTAAATCCTGATAATAGTGATGTGGACAAACTATTTATCCAGTTGGTACAAACCTACAATCAATTATTTGAAGAAAACCCTATTAACGCAAGTGGAGTAGATGCTAAAGCGATTCTTTCTGCACGATTGAGTAAATCAAGACGATTAGAAAATCTCATTGCTCAGCTCCCCGGTGAGAAGAAAAATGGCTTATTTGGGAATCTCATTGCTTTGTCATTGGGTTTGACCCCTAATTTTAAATCAAATTTTGATTTGGCAGAAGATGCTAAATTACAGCTTTCAAAAGATACTTACGATGATGATTTAGATAATTTATTGGCGCAAATTGGAGATCAATATGCTGATTTGTTTTTGGCAGCTAAGAATTTATCAGATGCTATTTTACTTTCAGATATCCTAAGAGTAAATACTGAAATAACTAAGGCTCCCCTATCAGCTTCAATGATTAAACGCTACGATGAACATCATCAAGACTTGACTCTTTTAAAAGCTTTAGTTCGACAACAACTTCCAGAAAAGTATAAAGAAATCTTTTTTGATCAATCAAAAAACGGATATGCAGGTTATATTGATGGGGGAGCTAGCCAAGAAGAATTTTATAAATTTATCAAACCAATTTTAGAAAAAATGGATGGTACTGAGGAATTATTGGTGAAACTAAATCGTGAAGATTTGCTGCGCAAGCAACGGACCTTTGACAACGGCTCTATTCCCCATCAAATTCACTTGGGTGAGCTGCATGCTATTTTGAGAAGACAAGAAGACTTTTATCCATTTTTAAAAGACAATCGTGAGAAGATTGAAAAAATCTTGACTTTTCGAATTCCTTATTATGTTGGTCCATTGGCGCGTGGCAATAGTCGTTTTGCATGGATGACTCGGAAGTCTGAAGAAACAATTACCCCATGGAATTTTGAAGAAGTTGTCGATAAAGGTGCTTCAGCTCAATCATTTATTGAACGCATGACAAACTTTGATAAAAATCTTCCAAATGAAAAAGTACTACCAAAACATAGTTTGCTTTATGAGTATTTTACGGTTTATAACGAATTGACAAAGGTCAAATATGTTACTGAAGGAATGCGAAAACCAGCATTTCTTTCAGGTGAACAGAAGAAAGCCATTGTTGATTTACTCTTCAAAACAAATCGAAAAGTAACCGTTAAGCAATTAAAAGAAGATTATTTCAAAAAAATAGAATGTTTTGATAGTGTTGAAATTTCAGGAGTTGAAGATAGATTTAATGCTTCATTAGGTACCTACCATGATTTGCTAAAAATTATTAAAGATAAAGATTTTTTGGATAATGAAGAAAATGAAGATATCTTAGAGGATATTGTTTTAACATTGACCTTATTTGAAGATAGGGAGATGATTGAGGAAAGACTTAAAACATATGCTCACCTCTTTGATGATAAGGTGATGAAACAGCTTAAACGTCGCCGTTATACTGGTTGGGGACGTTTGTCTCGAAAATTGATTAATGGTATTAGGGATAAGCAATCTGGCAAAACAATATTAGATTTTTTGAAATCAGATGGTTTTGCCAATCGCAATTTTATGCAGCTGATCCATGATGATAGTTTGACATTTAAAGAAGACATTCAAAAAGCACAAGTGTCTGGACAAGGCGATAGTTTACATGAACATATTGCAAATTTAGCTGGTAGCCCTGCTATTAAAAAAGGTATTTTACAGACTGTAAAAGTTGTTGATGAATTGGTCAAAGTAATGGGGCGGCATAAGCCAGAAAATATCGTTATTGAAATGGCACGTGAAAATCAGACAACTCAAAAGGGCCAGAAAAATTCGCGAGAGCGTATGAAACGAATCGAAGAAGGTATCAAAGAATTAGGAAGTCAGATTCTTAAAGAGCATCCTGTTGAAAATACTCAATTGCAAAATGAAAAGCTCTATCTCTATTATCTCCAAAATGGAAGAGACATGTATGTGGACCAAGAATTAGATATTAATCGTTTAAGTGATTATGATGTCGATCACATTGTTCCACAAAGTTTCCTTAAAGACGATTCAATAGACAATAAGGTCTTAACGCGTTCTGATAAAAATCGTGGTAAATCGGATAACGTTCCAAGTGAAGAAGTAGTCAAAAAGATGAAAAACTATTGGAGACAACTTCTAAACGCCAAGTTAATCACTCAACGTAAGTTTGATAATTTAACGAAAGCTGAACGTGGAGGTTTGAGTGAACTTGATAAAGCTGGTTTTATCAAACGCCAATTGGTTGAAACTCGCCAAATCACTAAGCATGTGGCACAAATTTTGGATAGTCGCATGAATACTAAATACGATGAAAATGATAAACTTATTCGAGAGGTTAAAGTGATTACCTTAAAATCTAAATTAGTTTCTGACTTCCGAAAAGATTTCCAATTCTATAAAGTACGTGAGATTAACAATTACCATCATGCCCATGATGCGTATCTAAATGCCGTCGTTGGAACTGCTTTGATTAAGAAATATCCAAAACTTGAATCGGAGTTTGTCTATGGTGATTATAAAGTTTATGATGTTCGTAAAATGATTGCTAAGTCTGAGCAAGAAATAGGCAAAGCAACCGCAAAATATTTCTTTTACTCTAATATCATGAACTTCTTCAAAACAGAAATTACACTTGCAAATGGAGAGATTCGCAAACGCCCTCTAATCGAAACTAATGGGGAAACTGGAGAAATTGTCTGGGATAAAGGGCGAGATTTTGCCACAGTGCGCAAAGTATTGTCCATGCCCCAAGTCAATATTGTCAAGAAAACAGAAGTACAGACAGGCGGATTCTCCAAGGAGTCAATTTTACCAAAAAGAAATTCGGACAAGCTTATTGCTCGTAAAAAAGACTGGGATCCAAAAAAATATGGTGGTTTTGATAGTCCAACGGTAGCTTATTCAGTCCTAGTGGTTGCTAAGGTGGAAAAAGGGAAATCGAAGAAGTTAAAATCCGTTAAAGAGTTACTAGGGATCACAATTATGGAAAGAAGTTCCTTTGAAAAAAATCCGATTGACTTTTTAGAAGCTAAAGGATATAAGGAAGTTAAAAAAGACTTAATCATTAAACTACCTAAATATAGTCTTTTTGAGTTAGAAAACGGTCGTAAACGGATGCTGGCTAGTGCCGGAGAATTACAAAAAGGAAATGAGCTGGCTCTGCCAAGCAAATATGTGAATTTTTTATATTTAGCTAGTCATTATGAAAAGTTGAAGGGTAGTCCAGAAGATAACGAACAAAAACAATTGTTTGTGGAGCAGCATAAGCATTATTTAGATGAGATTATTGAGCAAATCAGTGAATTTTCTAAGCGTGTTATTTTAGCAGATGCCAATTTAGATAAAGTTCTTAGTGCATATAACAAACATAGAGACAAACCAATACGTGAACAAGCAGAAAATATTATTCATTTATTTACGTTGACGAATCTTGGAGCTCCCGCTGCTTTTAAATATTTTGATACAACAATTGATCGTAAACGATATACGTCTACAAAAGAAGTTTTAGATGCCACTCTTATCCATCAATCCATCACTGGTCTTTATGAAACACGCATTGATTTGAGTCAGCTAGGAGGTGACTGATAATCAAATGTCAGACGAAAATGCCAATTATTGAAGCGGCTAACGCCGCTTTTTTTGTTTCTGGTCTCCCTTGCTTGTACTTTACAGTATAGCTTCTAGAGATCTGCAGTGACTGGAGCTTCTAGAGATCAGGTCAGACGCGATTTCCTGGGTGCTCGAGCCATGGGAAAGCGGTGGTGGAAAAAACGCCGAATGAAGCGGATGAAATTGCTCATCGTCTCGTGAAAAAGCCGAAGAAGGTTAAGCCTGGGTATAAAAAGAAAATGAGCTATGAGATGGAGAAATTGAAGTCATGCGCCGGTTAGTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTTTTTTTCTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCCTCAATGATCCGACAGGAAGTGGTATTAGCGACTCCTACAAGGAATAGGTGTCTGGGTCATGCAGTGACTGGGAAAACCCTGGCGACTAGTCTTGGACTCCTGTTGATAGATCCAGTAATGACCTCAGAACTCCATCTGGATTTGTTCAGAACGCTCGGTTGCCGCCGGGCGTTTTTTATTGGTGAGAATCCAGGGGTCCCCAATAATTACGATTTAAATCCTTCAAACTTCCCAAAGGCGAGCCCTAGTGACATTAGAAAACCGACTGTAAAAAGTACAGTCGGCATTATCTCATATTATAAAAGCCAGTCATTAGGCCTATCTGACAATTCCTGAATAGAGTTCATAAACAATCCTGCATGATAACCATCACAAACAGAATGATGTACCTGTAAAGATAGCGGTAAATATATTGAATTACCTTTATTAATGAATTTTCCTGCTGTAATAATGGGTAGAAGGTAATTACTATTATTATTGATATTTAAGTTAAACCCAGTAAATGAAGTCCATGGAATAATAGAAAGAGAAAAAGCATTTTCAGGTATAGGTGTTTTGGGAAACAATTTCCCCGAACCATTATATTTCTCTACATCAGAAAGGTATAAATCATAAAACTCTTTGAAGTCATTCTTTACAGGAGTCCAAATACCAGAGAATGTTTTAGATACACCATCAAAAATTGTATAAAGTGGCTCTAACTTATCCCAATAACCTAACTCTCCGTCGCTATTGTAACCAGTTCTAAAAGCTGTATTTGAGTTTATCACCCTTGTCACTAAGAAAATAAATGCAGGGTAAAATTTATATCCTTCTTGTTTTATGTTTCGGTATAAAACACTAATATCAATTTCTGTGGTTATACTAAAAGTCGTTTGTTGGTTCAAATAATGATTAAATATCTCTTTTCTCTTCCAATTGTCTAAATCAATTTTATTAAAGTTCATTTGATATGCCTCCTAAATTTTTATCTAAAGTGAATTTAGGAGGCTTACTTGTCTGCTTTCTTCATTAGAATCAATCCTTTTTTAAAAGTCAATCCCGTTTGTTGAAGACTTTTGTCCTTTTCCGCTGCATAAACAATATGGCCCGTTTGTTGAACTACTCTTTAATAAAATAATTTTTCCGTTCCCAATTCCACATTGCAATAATAGAAAATCCATCTTCATCGGCTTTTTCGTCATCATCTGTATGAATCAAATCGCCTTCTTCTGTGTCATCAAGGTTTAATTTTTTATGTATTTCTTTTAACAAACCACCATAGGAGATTAACCTTTTACGGTGTAAACCTTCCTCCAAATCAGACAAACGTTTCAAATTCTTTTCTTCATCATCGGTCATAAAATCCGTATCCTTTACAGGATATTTTGCAGTTTCGTCAATTGCCGATTGTATATCCGATTTATATTTATTTTTCGGTCGAATCATTTGAACTTTTACATTTGGATCATAGTCTAATTTCATTGCCTTTTTCCAAAATTGAATCCATTGTTTTTGATTCACGTAGTTTTCTGTATTCTTAAAATAAGTTGGTTCCACACATACCAATACATGCATGTGCTGATTATAAGAATTATCTTTATTATTTATTGTCACTTCCGTTGCACGCATAAAACCAACAAGATTTTTATTAATTTTTTTATATTGCATCATTCGGCGAAATCCTTGAGCCATATCTGACAAACTCTTATTTAATTCTTCGCCATCATAAACATTTTTAACTGTTAATGTGAGAAACAACCAACGAACTGTTGGCTTTTGTTTAATAACTTCAGCAACAACCTTTTGTGACTGAATGCCATGTTTCATTGCTCTCCTCCAGTTGCACATTGGACAAAGCCTGGATTTACAAAACCACACTCGATACAACTTTCTTTCGCCTGTTTCACGATTTTGTTTATACTCTAATATTTCAGCACAATCTTTTACTCTTTCAGCCTTTTTAAATTCAAGAATATGCAGAAGTTCAAAGTAATCAACATTAGCGATTTTCTTTTCTCTCCATGGTCTCACTTTTCCACTTTTTGTCTTGTCCACTAAAACCCTTGATTTTTCATCTGAATAAATGCTACTATTAGGACACATAATATTAAAAGAAACCCCCATCTATTTAGTTATTTGTTTGGTCACTTATAACTTTAACAGATGGGGTTTTTCTGTGCAACCAATTTTAAGGGTTTTCCAATACTTTAAAACACATACATACCAACACTTCAACGCACCTTTCAGCAACTAAAATAAAAATGACGTTATTTCTATATGTATCAAGATAAGAAAGAACAAGTTCAAAACCATCAAAAAAAGACACCTTTTCAGGTGCTTTTTTTATTTTATAAACTCATTCCCTGATCTCGACTTCGTTCTTTTTTTACCTCTCGGTTATGAGTTAGTTCAAATTCGTTCTTTTTAGGTTCTAAATCGTGTTTTTCTTGGAATTGTGCTGTTTTATCCTTTACCTTGTCTACAAACCCCTTAAAAACGTTTTTAAAGGCTTTTAAGCGTCTGTACGTTCCTTAAGGAATTATTCCTTAGTGCTTTCTAGGTTAATGTCATGATAATAATGGTTTCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTCCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTGTTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGCAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCTTAATAAGATGATCTTCTTGAGATCGTTTTGGTCTGCGCGTAATCTCTTGCTCTGAAAACGAAAAAACCGCCTTGCAGGGAGGTTTTTCGAAGGTTCTCTGAGCTACCAACTCTTTGAACCGAGGTAACTGGCTTGCAGGAGCGCAGTCACCAAAACTTGTCCTTTCAGTTTAGCCTTAACCGGCGCATGACTTCAAGACTAACTCCTCTAAATCAATTACCAGTGGCTGCTGCCAGTGGTGCTTTTGCATGTCTTTCCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGACTGAACGGGGGGTTCGTGCATACAGTCCAGCTTGGAGCGAACTGCCTACCCGGAACTGAGTGTCAGGCGTGGAATGAGACAAACGCGGCCATAACAGCGGAATGACACCGGTAAACCGAAAGGCAGGAACAGGAGAGCGCACGAGGGAGCCGCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCACTGATTTGAGCGTCAGATTTCGTGATGCTTGTCAGGGGGCGGAGCCTATGGAAAAACGCTTTGCCCGAGCCTATGGAAAAACGCTTTGCCCCACACAGGCTCTTGAACAAGGGATAACAATTTGTCATAGCTGTATTCGTTACAAGGAGGATTTTCGAAAAAACACCCTAACGGGTGTTTTTTTATAGCTGGTCTCCCCAAGTGCTGTAAAAAACGCCGAATGAAGCGGATGAAATTGCTCATCGTCTCGTGAAAAAGCCGAAGAAGGTTAAGCCTGGGTATAAAAAGAAAATGAGCTATGAGATGGAGAAAGCCATAACCATGAGTGATAACACTGGTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTTTTTTTCTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCCTCAATGATC >pCas9g1-D15-mut (SEQ ID No: 237)GAGTAAATCCTGGGGCAAATTCATCGAGGAGGAAGAGGCGGAAATGGCTTCCCGTCGTAATCTAATGATTGTCGATGGAACTAACTTAGGCTTTCGCTTCAAACATAACAATAGTAAAAAACCATTTGCCTCAAGTTATGTTTCAACTATTCAATCTCTGGCAAAATCCTACTCTGCCAGAACTACGATTGTTCTAGGTGATAAGGGCAAAAGCGTGTTCAGACTAGAACATCTACCAGAGTATAAAGGTAATCGTGATGAAAAGTACGCACAACGTACGGAAGAGGAGAAAGCGCTAGATGAGCAGTTCTTCGAATACCTCAAAGATGCTTTCGAGTTGTGTAAAACTACATTCCCAACTTTTACCATTCGTGGTGTAGAAGCAGATGACATGGCGGCGTATATTGTTAAGCTCATCGGGCATCTTTATGATCACGTTTGGCTAATATCTACAGATGGTGACTGGGATACTTTATTAACGGATAAAGTTTCTCGTTTTTCTTTCACAACACGTCGTGAGTATCATCTTCGTGATATGTATGAGCACCATAACGTGGACGACGTAGAACAGTTTATCTCCCTGAAAGCAATTATGGGAGATCTAGGAGATAATATTCGTGGTGTTGAAGGAATAGGAGCAAAACGCGGATATAATATTATTCGTGAGTTTGGTAACGTACTGGATATTATTGATCAGCTTCCACTGCCTGGAAAGCAGAAATATATACAGAACCTGAATGCATCGGAAGAACTGCTTTTCCGAAACTTGATTCTGGTTGATTTACCTACCTACTGTGTGGATGCTATTGCTGCTGTAGGTCAAGATGTGTTAGATAAGTTCACGAAAGACATCCTTGAGATCGCGGAACAATGATAAGCTCTTAAAGGGGGTTTTAGATACCAGAGATGGATAAGAAATACTCAATAGGCTTAGATATCGGCACAAATAGCGTCGGATGGGCGGTGATCACTGATGAATATAAGGTTCCGTCTAAAAAGTTCAAGGTTCTGGGAAATACAGACCGCCACAGTATCAAAAAAAATCTTATAGGGGCTCTTTTATTTGACAGTGGAGAGACAGCGGAAGCGACTCGTCTCAAACGGACAGCTCGTAGAAGGTATACACGTCGGAAGAATCGTATTTGTTATCTACAGGAGATTTTTTCAAATGAGATGGCGAAAGTAGATGATAGTTTCTTTCATCGACTTGAAGAGTCTTTTTTGGTGGAAGAAGACAAGAAGCATGAACGTCATCCTATTTTTGGAAATATAGTAGATGAAGTTGCTTATCATGAGAAATATCCAACTATCTATCATCTGCGAAAAAAATTGGTAGATTCTACTGATAAAGCGGATTTGCGCTTAATCTATTTGGCCTTAGCGCATATGATTAAGTTTCGTGGTCATTTTTTGATTGAGGGAGATTTAAATCCTGATAATAGTGATGTGGACAAACTATTTATCCAGTTGGTACAAACCTACAATCAATTATTTGAAGAAAACCCTATTAACGCAAGTGGAGTAGATGCTAAAGCGATTCTTTCTGCACGATTGAGTAAATCAAGACGATTAGAAAATCTCATTGCTCAGCTCCCCGGTGAGAAGAAAAATGGCTTATTTGGGAATCTCATTGCTTTGTCATTGGGTTTGACCCCTAATTTTAAATCAAATTTTGATTTGGCAGAAGATGCTAAATTACAGCTTTCAAAAGATACTTACGATGATGATTTAGATAATTTATTGGCGCAAATTGGAGATCAATATGCTGATTTGTTTTTGGCAGCTAAGAATTTATCAGATGCTATTTTACTTTCAGATATCCTAAGAGTAAATACTGAAATAACTAAGGCTCCCCTATCAGCTTCAATGATTAAACGCTACGATGAACATCATCAAGACTTGACTCTTTTAAAAGCTTTAGTTCGACAACAACTTCCAGAAAAGTATAAAGAAATCTTTTTTGATCAATCAAAAAACGGATATGCAGGTTATATTGATGGGGGAGCTAGCCAAGAAGAATTTTATAAATTTATCAAACCAATTTTAGAAAAAATGGATGGTACTGAGGAATTATTGGTGAAACTAAATCGTGAAGATTTGCTGCGCAAGCAACGGACCTTTGACAACGGCTCTATTCCCCATCAAATTCACTTGGGTGAGCTGCATGCTATTTTGAGAAGACAAGAAGACTTTTATCCATTTTTAAAAGACAATCGTGAGAAGATTGAAAAAATCTTGACTTTTCGAATTCCTTATTATGTTGGTCCATTGGCGCGTGGCAATAGTCGTTTTGCATGGATGACTCGGAAGTCTGAAGAAACAATTACCCCATGGAATTTTGAAGAAGTTGTCGATAAAGGTGCTTCAGCTCAATCATTTATTGAACGCATGACAAACTTTGATAAAAATCTTCCAAATGAAAAAGTACTACCAAAACATAGTTTGCTTTATGAGTATTTTACGGTTTATAACGAATTGACAAAGGTCAAATATGTTACTGAAGGAATGCGAAAACCAGCATTTCTTTCAGGTGAACAGAAGAAAGCCATTGTTGATTTACTCTTCAAAACAAATCGAAAAGTAACCGTTAAGCAATTAAAAGAAGATTATTTCAAAAAAATAGAATGTTTTGATAGTGTTGAAATTTCAGGAGTTGAAGATAGATTTAATGCTTCATTAGGTACCTACCATGATTTGCTAAAAATTATTAAAGATAAAGATTTTTTGGATAATGAAGAAAATGAAGATATCTTAGAGGATATTGTTTTAACATTGACCTTATTTGAAGATAGGGAGATGATTGAGGAAAGACTTAAAACATATGCTCACCTCTTTGATGATAAGGTGATGAAACAGCTTAAACGTCGCCGTTATACTGGTTGGGGACGTTTGTCTCGAAAATTGATTAATGGTATTAGGGATAAGCAATCTGGCAAAACAATATTAGATTTTTTGAAATCAGATGGTTTTGCCAATCGCAATTTTATGCAGCTGATCCATGATGATAGTTTGACATTTAAAGAAGACATTCAAAAAGCACAAGTGTCTGGACAAGGCGATAGTTTACATGAACATATTGCAAATTTAGCTGGTAGCCCTGCTATTAAAAAAGGTATTTTACAGACTGTAAAAGTTGTTGATGAATTGGTCAAAGTAATGGGGCGGCATAAGCCAGAAAATATCGTTATTGAAATGGCACGTGAAAATCAGACAACTCAAAAGGGCCAGAAAAATTCGCGAGAGCGTATGAAACGAATCGAAGAAGGTATCAAAGAATTAGGAAGTCAGATTCTTAAAGAGCATCCTGTTGAAAATACTCAATTGCAAAATGAAAAGCTCTATCTCTATTATCTCCAAAATGGAAGAGACATGTATGTGGACCAAGAATTAGATATTAATCGTTTAAGTGATTATGATGTCGATCACATTGTTCCACAAAGTTTCCTTAAAGACGATTCAATAGACAATAAGGTCTTAACGCGTTCTGATAAAAATCGTGGTAAATCGGATAACGTTCCAAGTGAAGAAGTAGTCAAAAAGATGAAAAACTATTGGAGACAACTTCTAAACGCCAAGTTAATCACTCAACGTAAGTTTGATAATTTAACGAAAGCTGAACGTGGAGGTTTGAGTGAACTTGATAAAGCTGGTTTTATCAAACGCCAATTGGTTGAAACTCGCCAAATCACTAAGCATGTGGCACAAATTTTGGATAGTCGCATGAATACTAAATACGATGAAAATGATAAACTTATTCGAGAGGTTAAAGTGATTACCTTAAAATCTAAATTAGTTTCTGACTTCCGAAAAGATTTCCAATTCTATAAAGTACGTGAGATTAACAATTACCATCATGCCCATGATGCGTATCTAAATGCCGTCGTTGGAACTGCTTTGATTAAGAAATATCCAAAACTTGAATCGGAGTTTGTCTATGGTGATTATAAAGTTTATGATGTTCGTAAAATGATTGCTAAGTCTGAGCAAGAAATAGGCAAAGCAACCGCAAAATATTTCTTTTACTCTAATATCATGAACTTCTTCAAAACAGAAATTACACTTGCAAATGGAGAGATTCGCAAACGCCCTCTAATCGAAACTAATGGGGAAACTGGAGAAATTGTCTGGGATAAAGGGCGAGATTTTGCCACAGTGCGCAAAGTATTGTCCATGCCCCAAGTCAATATTGTCAAGAAAACAGAAGTACAGACAGGCGGATTCTCCAAGGAGTCAATTTTACCAAAAAGAAATTCGGACAAGCTTATTGCTCGTAAAAAAGACTGGGATCCAAAAAAATATGGTGGTTTTGATAGTCCAACGGTAGCTTATTCAGTCCTAGTGGTTGCTAAGGTGGAAAAAGGGAAATCGAAGAAGTTAAAATCCGTTAAAGAGTTACTAGGGATCACAATTATGGAAAGAAGTTCCTTTGAAAAAAATCCGATTGACTTTTTAGAAGCTAAAGGATATAAGGAAGTTAAAAAAGACTTAATCATTAAACTACCTAAATATAGTCTTTTTGAGTTAGAAAACGGTCGTAAACGGATGCTGGCTAGTGCCGGAGAATTACAAAAAGGAAATGAGCTGGCTCTGCCAAGCAAATATGTGAATTTTTTATATTTAGCTAGTCATTATGAAAAGTTGAAGGGTAGTCCAGAAGATAACGAACAAAAACAATTGTTTGTGGAGCAGCATAAGCATTATTTAGATGAGATTATTGAGCAAATCAGTGAATTTTCTAAGCGTGTTATTTTAGCAGATGCCAATTTAGATAAAGTTCTTAGTGCATATAACAAACATAGAGACAAACCAATACGTGAACAAGCAGAAAATATTATTCATTTATTTACGTTGACGAATCTTGGAGCTCCCGCTGCTTTTAAATATTTTGATACAACAATTGATCGTAAACGATATACGTCTACAAAAGAAGTTTTAGATGCCACTCTTATCCATCAATCCATCACTGGTCTTTATGAAACACGCATTGATTTGAGTCAGCTAGGAGGTGACTGATAATCAAATGTCAGACGAAAATGCCAATTATTGAAGCGGCTAACGCCGCTTTTTTTGTTTCTGGTCTCCCTTGCTTGTACTTTACAGTATAGCTTCTAGAGATCTGCAGTGACTGGAGCTTCTAGAGATCTGCAGTGACTGGGAAAACCCTGGCGACTAGTCTTGGACTCCTGTTGATAGATCCAGTAATGACCTCAGAACTCCATCTGGATTTGTTCAGAACGCTCGGTTGCCGCCGGGCGTTTTTTATTGGTGAGAATCCAGGGGTCCCCAATAATTACGATTTAAATCCTTCAAACTTCCCAAAGGCGAGCCCTAGTGACATTAGAAAACCGACTGTAAAAAGTACAGTCGGCATTATCTCATATTATAAAAGCCAGTCATTAGGCCTATCTGACAATTCCTGAATAGAGTTCATAAACAATCCTGCATGATAACCATCACAAACAGAATGATGTACCTGTAAAGATAGCGGTAAATATATTGAATTACCTTTATTAATGAATTTTCCTGCTGTAATAATGGGTAGAAGGTAATTACTATTATTATTGATATTTAAGTTAAACCCAGTAAATGAAGTCCATGGAATAATAGAAAGAGAAAAAGCATTTTCAGGTATAGGTGTTTTGGGAAACAATTTCCCCGAACCATTATATTTCTCTACATCAGAAAGGTATAAATCATAAAACTCTTTGAAGTCATTCTTTACAGGAGTCCAAATACCAGAGAATGTTTTAGATACACCATCAAAAATTGTATAAAGTGGCTCTAACTTATCCCAATAACCTAACTCTCCGTCGCTATTGTAACCAGTTCTAAAAGCTGTATTTGAGTTTATCACCCTTGTCACTAAGAAAATAAATGCAGGGTAAAATTTATATCCTTCTTGTTTTATGTTTCGGTATAAAACACTAATATCAATTTCTGTGGTTATACTAAAAGTCGTTTGTTGGTTCAAATAATGATTAAATATCTCTTTTCTCTTCCAATTGTCTAAATCAATTTTATTAAAGTTCATTTGATATGCCTCCTAAATTTTTATCTAAAGTGAATTTAGGAGGCTTACTTGTCTGCTTTCTTCATTAGAATCAATCCTTTTTTAAAAGTCAATCCCGTTTGTTGAAGACTTTTGTCCTTTTCCGCTGCATAAACAATATGGCCCGTTTGTTGAACTACTCTTTAATAAAATAATTTTTCCGTTCCCAATTCCACATTGCAATAATAGAAAATCCATCTTCATCGGCTTTTTCGTCATCATCTGTATGAATCAAATCGCCTTCTTCTGTGTCATCAAGGTTTAATTTTTTATGTATTTCTTTTAACAAACCACCATAGGAGATTAACCTTTTACGGTGTAAACCTTCCTCCAAATCAGACAAACGTTTCAAATTCTTTTCTTCATCATCGGTCATAAAATCCGTATCCTTTACAGGATATTTTGCAGTTTCGTCAATTGCCGATTGTATATCCGATTTATATTTATTTTTCGGTCGAATCATTTGAACTTTTACATTTGGATCATAGTCTAATTTCATTGCCTTTTTCCAAAATTGAATCCATTGTTTTTGATTCACGTAGTTTTCTGTATTCTTAAAATAAGTTGGTTCCACACATACCAATACATGCATGTGCTGATTATAAGAATTATCTTTATTATTTATTGTCACTTCCGTTGCACGCATAAAACCAACAAGATTTTTATTAATTTTTTTATATTGCATCATTCGGCGAAATCCTTGAGCCATATCTGACAAACTCTTATTTAATTCTTCGCCATCATAAACATTTTTAACTGTTAATGTGAGAAACAACCAACGAACTGTTGGCTTTTGTTTAATAACTTCAGCAACAACCTTTTGTGACTGAATGCCATGTTTCATTGCTCTCCTCCAGTTGCACATTGGACAAAGCCTGGATTTACAAAACCACACTCGATACAACTTTCTTTCGCCTGTTTCACGATTTTGTTTATACTCTAATATTTCAGCACAATCTTTTACTCTTTCAGCCTTTTTAAATTCAAGAATATGCAGAAGTTCAAAGTAATCAACATTAGCGATTTTCTTTTCTCTCCATGGTCTCACTTTTCCACTTTTTGTCTTGTCCACTAAAACCCTTGATTTTTCATCTGAATAAATGCTACTATTAGGACACATAATATTAAAAGAAACCCCCATCTATTTAGTTATTTGTTTGGTCACTTATAACTTTAACAGATGGGGTTTTTCTGTGCAACCAATTTTAAGGGTTTTCCAATACTTTAAAACACATACATACCAACACTTCAACGCACCTTTCAGCAACTAAAATAAAAATGACGTTATTTCTATATGTATCAAGATAAGAAAGAACAAGTTCAAAACCATCAAAAAAAGACACCTTTTCAGGTGCTTTTTTTATTTTATAAACTCATTCCCTGATCTCGACTTCGTTCTTTTTTTACCTCTCGGTTATGAGTTAGTTCAAATTCGTTCTTTTTAGGTTCTAAATCGTGTTTTTCTTGGAATTGTGCTGTTTTATCCTTTACCTTGTCTACAAACCCCTTAAAAACGTTTTTAAAGGCTTTTAAGCGTCTGTACGTTCCTTAAGGAATTATTCCTTAGTGCTTTCTAGGTTAATGTCATGATAATAATGGTTTCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTCCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTGTTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGCAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCTTAATAAGATGATCTTCTTGAGATCGTTTTGGTCTGCGCGTAATCTCTTGCTCTGAAAACGAAAAAACCGCCTTGCAGGGAGGTTTTTCGAAGGTTCTCTGAGCTACCAACTCTTTGAACCGAGGTAACTGGCTTGCAGGAGCGCAGTCACCAAAACTTGTCCTTTCAGTTTAGCCTTAACCGGCGCATGACTTCAAGACTAACTCCTCTAAATCAATTACCAGTGGCTGCTGCCAGTGGTGCTTTTGCATGTCTTTCCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGACTGAACGGGGGGTTCGTGCATACAGTCCAGCTTGGAGCGAACTGCCTACCCGGAACTGAGTGTCAGGCGTGGAATGAGACAAACGCGGCCATAACAGCGGAATGACACCGGTAAACCGAAAGGCAGGAACAGGAGAGCGCACGAGGGAGCCGCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCACTGATTTGAGCGTCAGATTTCGTGATGCTTGTCAGGGGGCGGAGCCTATGGAAAAACGCTTTGCCCGAGCCTATGGAAAAACGCTTTGCCCCACACAGGCTCTTGAACAAGGGATAACAATTTGTCATAGCTGTATTCGTTACAAGGAGGATTTTCGAAAAAACACCCTAACGGGTGTTTTTTTATAGCTGGTCTCCCCAAGTGCTGTAAAAAACGCCGAATGAAGCGGATGAAATTGCTCATCGTCTCGTGAAAAAGCCGAAGAAGGTTAAGCCTGGGTATAAAAAGAAAATGAGCTATGAGATGGAGAAAGCCATAACCATGAGTGATAACACTGGTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTTTTTTTCTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCCTCAATGATCTCCTTATCCGGTTAAGATGGC >pCas9g2-D15-mut (SEQ ID No: 238)GAGTAAATCCTGGGGCAAATTCATCGAGGAGGAAGAGGCGGAAATGGCTTCCCGTCGTAATCTAATGATTGTCGATGGAACTAACTTAGGCTTTCGCTTCAAACATAACAATAGTAAAAAACCATTTGCCTCAAGTTATGTTTCAACTATTCAATCTCTGGCAAAATCCTACTCTGCCAGAACTACGATTGTTCTAGGTGATAAGGGCAAAAGCGTGTTCAGACTAGAACATCTACCAGAGTATAAAGGTAATCGTGATGAAAAGTACGCACAACGTACGGAAGAGGAGAAAGCGCTAGATGAGCAGTTCTTCGAATACCTCAAAGATGCTTTCGAGTTGTGTAAAACTACATTCCCAACTTTTACCATTCGTGGTGTAGAAGCAGATGACATGGCGGCGTATATTGTTAAGCTCATCGGGCATCTTTATGATCACGTTTGGCTAATATCTACAGATGGTGACTGGGATACTTTATTAACGGATAAAGTTTCTCGTTTTTCTTTCACAACACGTCGTGAGTATCATCTTCGTGATATGTATGAGCACCATAACGTGGACGACGTAGAACAGTTTATCTCCCTGAAAGCAATTATGGGAGATCTAGGAGATAATATTCGTGGTGTTGAAGGAATAGGAGCAAAACGCGGATATAATATTATTCGTGAGTTTGGTAACGTACTGGATATTATTGATCAGCTTCCACTGCCTGGAAAGCAGAAATATATACAGAACCTGAATGCATCGGAAGAACTGCTTTTCCGAAACTTGATTCTGGTTGATTTACCTACCTACTGTGTGGATGCTATTGCTGCTGTAGGTCAAGATGTGTTAGATAAGTTCACGAAAGACATCCTTGAGATCGCGGAACAATGATAAGCTCTTAAAGGGGGTTTTAGATACCAGAGATGGATAAGAAATACTCAATAGGCTTAGATATCGGCACAAATAGCGTCGGATGGGCGGTGATCACTGATGAATATAAGGTTCCGTCTAAAAAGTTCAAGGTTCTGGGAAATACAGACCGCCACAGTATCAAAAAAAATCTTATAGGGGCTCTTTTATTTGACAGTGGAGAGACAGCGGAAGCGACTCGTCTCAAACGGACAGCTCGTAGAAGGTATACACGTCGGAAGAATCGTATTTGTTATCTACAGGAGATTTTTTCAAATGAGATGGCGAAAGTAGATGATAGTTTCTTTCATCGACTTGAAGAGTCTTTTTTGGTGGAAGAAGACAAGAAGCATGAACGTCATCCTATTTTTGGAAATATAGTAGATGAAGTTGCTTATCATGAGAAATATCCAACTATCTATCATCTGCGAAAAAAATTGGTAGATTCTACTGATAAAGCGGATTTGCGCTTAATCTATTTGGCCTTAGCGCATATGATTAAGTTTCGTGGTCATTTTTTGATTGAGGGAGATTTAAATCCTGATAATAGTGATGTGGACAAACTATTTATCCAGTTGGTACAAACCTACAATCAATTATTTGAAGAAAACCCTATTAACGCAAGTGGAGTAGATGCTAAAGCGATTCTTTCTGCACGATTGAGTAAATCAAGACGATTAGAAAATCTCATTGCTCAGCTCCCCGGTGAGAAGAAAAATGGCTTATTTGGGAATCTCATTGCTTTGTCATTGGGTTTGACCCCTAATTTTAAATCAAATTTTGATTTGGCAGAAGATGCTAAATTACAGCTTTCAAAAGATACTTACGATGATGATTTAGATAATTTATTGGCGCAAATTGGAGATCAATATGCTGATTTGTTTTTGGCAGCTAAGAATTTATCAGATGCTATTTTACTTTCAGATATCCTAAGAGTAAATACTGAAATAACTAAGGCTCCCCTATCAGCTTCAATGATTAAACGCTACGATGAACATCATCAAGACTTGACTCTTTTAAAAGCTTTAGTTCGACAACAACTTCCAGAAAAGTATAAAGAAATCTTTTTTGATCAATCAAAAAACGGATATGCAGGTTATATTGATGGGGGAGCTAGCCAAGAAGAATTTTATAAATTTATCAAACCAATTTTAGAAAAAATGGATGGTACTGAGGAATTATTGGTGAAACTAAATCGTGAAGATTTGCTGCGCAAGCAACGGACCTTTGACAACGGCTCTATTCCCCATCAAATTCACTTGGGTGAGCTGCATGCTATTTTGAGAAGACAAGAAGACTTTTATCCATTTTTAAAAGACAATCGTGAGAAGATTGAAAAAATCTTGACTTTTCGAATTCCTTATTATGTTGGTCCATTGGCGCGTGGCAATAGTCGTTTTGCATGGATGACTCGGAAGTCTGAAGAAACAATTACCCCATGGAATTTTGAAGAAGTTGTCGATAAAGGTGCTTCAGCTCAATCATTTATTGAACGCATGACAAACTTTGATAAAAATCTTCCAAATGAAAAAGTACTACCAAAACATAGTTTGCTTTATGAGTATTTTACGGTTTATAACGAATTGACAAAGGTCAAATATGTTACTGAAGGAATGCGAAAACCAGCATTTCTTTCAGGTGAACAGAAGAAAGCCATTGTTGATTTACTCTTCAAAACAAATCGAAAAGTAACCGTTAAGCAATTAAAAGAAGATTATTTCAAAAAAATAGAATGTTTTGATAGTGTTGAAATTTCAGGAGTTGAAGATAGATTTAATGCTTCATTAGGTACCTACCATGATTTGCTAAAAATTATTAAAGATAAAGATTTTTTGGATAATGAAGAAAATGAAGATATCTTAGAGGATATTGTTTTAACATTGACCTTATTTGAAGATAGGGAGATGATTGAGGAAAGACTTAAAACATATGCTCACCTCTTTGATGATAAGGTGATGAAACAGCTTAAACGTCGCCGTTATACTGGTTGGGGACGTTTGTCTCGAAAATTGATTAATGGTATTAGGGATAAGCAATCTGGCAAAACAATATTAGATTTTTTGAAATCAGATGGTTTTGCCAATCGCAATTTTATGCAGCTGATCCATGATGATAGTTTGACATTTAAAGAAGACATTCAAAAAGCACAAGTGTCTGGACAAGGCGATAGTTTACATGAACATATTGCAAATTTAGCTGGTAGCCCTGCTATTAAAAAAGGTATTTTACAGACTGTAAAAGTTGTTGATGAATTGGTCAAAGTAATGGGGCGGCATAAGCCAGAAAATATCGTTATTGAAATGGCACGTGAAAATCAGACAACTCAAAAGGGCCAGAAAAATTCGCGAGAGCGTATGAAACGAATCGAAGAAGGTATCAAAGAATTAGGAAGTCAGATTCTTAAAGAGCATCCTGTTGAAAATACTCAATTGCAAAATGAAAAGCTCTATCTCTATTATCTCCAAAATGGAAGAGACATGTATGTGGACCAAGAATTAGATATTAATCGTTTAAGTGATTATGATGTCGATCACATTGTTCCACAAAGTTTCCTTAAAGACGATTCAATAGACAATAAGGTCTTAACGCGTTCTGATAAAAATCGTGGTAAATCGGATAACGTTCCAAGTGAAGAAGTAGTCAAAAAGATGAAAAACTATTGGAGACAACTTCTAAACGCCAAGTTAATCACTCAACGTAAGTTTGATAATTTAACGAAAGCTGAACGTGGAGGTTTGAGTGAACTTGATAAAGCTGGTTTTATCAAACGCCAATTGGTTGAAACTCGCCAAATCACTAAGCATGTGGCACAAATTTTGGATAGTCGCATGAATACTAAATACGATGAAAATGATAAACTTATTCGAGAGGTTAAAGTGATTACCTTAAAATCTAAATTAGTTTCTGACTTCCGAAAAGATTTCCAATTCTATAAAGTACGTGAGATTAACAATTACCATCATGCCCATGATGCGTATCTAAATGCCGTCGTTGGAACTGCTTTGATTAAGAAATATCCAAAACTTGAATCGGAGTTTGTCTATGGTGATTATAAAGTTTATGATGTTCGTAAAATGATTGCTAAGTCTGAGCAAGAAATAGGCAAAGCAACCGCAAAATATTTCTTTTACTCTAATATCATGAACTTCTTCAAAACAGAAATTACACTTGCAAATGGAGAGATTCGCAAACGCCCTCTAATCGAAACTAATGGGGAAACTGGAGAAATTGTCTGGGATAAAGGGCGAGATTTTGCCACAGTGCGCAAAGTATTGTCCATGCCCCAAGTCAATATTGTCAAGAAAACAGAAGTACAGACAGGCGGATTCTCCAAGGAGTCAATTTTACCAAAAAGAAATTCGGACAAGCTTATTGCTCGTAAAAAAGACTGGGATCCAAAAAAATATGGTGGTTTTGATAGTCCAACGGTAGCTTATTCAGTCCTAGTGGTTGCTAAGGTGGAAAAAGGGAAATCGAAGAAGTTAAAATCCGTTAAAGAGTTACTAGGGATCACAATTATGGAAAGAAGTTCCTTTGAAAAAAATCCGATTGACTTTTTAGAAGCTAAAGGATATAAGGAAGTTAAAAAAGACTTAATCATTAAACTACCTAAATATAGTCTTTTTGAGTTAGAAAACGGTCGTAAACGGATGCTGGCTAGTGCCGGAGAATTACAAAAAGGAAATGAGCTGGCTCTGCCAAGCAAATATGTGAATTTTTTATATTTAGCTAGTCATTATGAAAAGTTGAAGGGTAGTCCAGAAGATAACGAACAAAAACAATTGTTTGTGGAGCAGCATAAGCATTATTTAGATGAGATTATTGAGCAAATCAGTGAATTTTCTAAGCGTGTTATTTTAGCAGATGCCAATTTAGATAAAGTTCTTAGTGCATATAACAAACATAGAGACAAACCAATACGTGAACAAGCAGAAAATATTATTCATTTATTTACGTTGACGAATCTTGGAGCTCCCGCTGCTTTTAAATATTTTGATACAACAATTGATCGTAAACGATATACGTCTACAAAAGAAGTTTTAGATGCCACTCTTATCCATCAATCCATCACTGGTCTTTATGAAACACGCATTGATTTGAGTCAGCTAGGAGGTGACTGATAATCAAATGTCAGACGAAAATGCCAATTATTGAAGCGGCTAACGCCGCTTTTTTTGTTTCTGGTCTCCCTTGCTTGTACTTTACAGTATAGCTTCTAGAGATCTGCAGTGACTGGAGCTTCTAGAGATCAGGTCAGACGCGATTTCCTGGGTGCTCGAGCCATGGGAAAGCGGTGGTGGAAAAAACGCCGAATGAAGCGGATGAAATTGCTCATCGTCTCGTGAAAAAGCCGAAGAAGGTTAAGCCTGGGTATAAAAAGAAAATGAGCTATGAGATGGAGAAATTGAAGTCATGCGCCGGTTAGTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTTTTTTTCTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCCTCAATGATCCGACAGGAAGTGGTATTAGCGACTCCTACAAGGAATAGGTGTCTGGGTCATGCAGTGACTGGGAAAACCCTGGCGACTAGTCTTGGACTCCTGTTGATAGATCCAGTAATGACCTCAGAACTCCATCTGGATTTGTTCAGAACGCTCGGTTGCCGCCGGGCGTTTTTTATTGGTGAGAATCCAGGGGTCCCCAATAATTACGATTTAAATCCTTCAAACTTCCCAAAGGCGAGCCCTAGTGACATTAGAAAACCGACTGTAAAAAGTACAGTCGGCATTATCTCATATTATAAAAGCCAGTCATTAGGCCTATCTGACAATTCCTGAATAGAGTTCATAAACAATCCTGCATGATAACCATCACAAACAGAATGATGTACCTGTAAAGATAGCGGTAAATATATTGAATTACCTTTATTAATGAATTTTCCTGCTGTAATAATGGGTAGAAGGTAATTACTATTATTATTGATATTTAAGTTAAACCCAGTAAATGAAGTCCATGGAATAATAGAAAGAGAAAAAGCATTTTCAGGTATAGGTGTTTTGGGAAACAATTTCCCCGAACCATTATATTTCTCTACATCAGAAAGGTATAAATCATAAAACTCTTTGAAGTCATTCTTTACAGGAGTCCAAATACCAGAGAATGTTTTAGATACACCATCAAAAATTGTATAAAGTGGCTCTAACTTATCCCAATAACCTAACTCTCCGTCGCTATTGTAACCAGTTCTAAAAGCTGTATTTGAGTTTATCACCCTTGTCACTAAGAAAATAAATGCAGGGTAAAATTTATATCCTTCTTGTTTTATGTTTCGGTATAAAACACTAATATCAATTTCTGTGGTTATACTAAAAGTCGTTTGTTGGTTCAAATAATGATTAAATATCTCTTTTCTCTTCCAATTGTCTAAATCAATTTTATTAAAGTTCATTTGATATGCCTCCTAAATTTTTATCTAAAGTGAATTTAGGAGGCTTACTTGTCTGCTTTCTTCATTAGAATCAATCCTTTTTTAAAAGTCAATCCCGTTTGTTGAAGACTTTTGTCCTTTTCCGCTGCATAAACAATATGGCCCGTTTGTTGAACTACTCTTTAATAAAATAATTTTTCCGTTCCCAATTCCACATTGCAATAATAGAAAATCCATCTTCATCGGCTTTTTCGTCATCATCTGTATGAATCAAATCGCCTTCTTCTGTGTCATCAAGGTTTAATTTTTTATGTATTTCTTTTAACAAACCACCATAGGAGATTAACCTTTTACGGTGTAAACCTTCCTCCAAATCAGACAAACGTTTCAAATTCTTTTCTTCATCATCGGTCATAAAATCCGTATCCTTTACAGGATATTTTGCAGTTTCGTCAATTGCCGATTGTATATCCGATTTATATTTATTTTTCGGTCGAATCATTTGAACTTTTACATTTGGATCATAGTCTAATTTCATTGCCTTTTTCCAAAATTGAATCCATTGTTTTTGATTCACGTAGTTTTCTGTATTCTTAAAATAAGTTGGTTCCACACATACCAATACATGCATGTGCTGATTATAAGAATTATCTTTATTATTTATTGTCACTTCCGTTGCACGCATAAAACCAACAAGATTTTTATTAATTTTTTTATATTGCATCATTCGGCGAAATCCTTGAGCCATATCTGACAAACTCTTATTTAATTCTTCGCCATCATAAACATTTTTAACTGTTAATGTGAGAAACAACCAACGAACTGTTGGCTTTTGTTTAATAACTTCAGCAACAACCTTTTGTGACTGAATGCCATGTTTCATTGCTCTCCTCCAGTTGCACATTGGACAAAGCCTGGATTTACAAAACCACACTCGATACAACTTTCTTTCGCCTGTTTCACGATTTTGTTTATACTCTAATATTTCAGCACAATCTTTTACTCTTTCAGCCTTTTTAAATTCAAGAATATGCAGAAGTTCAAAGTAATCAACATTAGCGATTTTCTTTTCTCTCCATGGTCTCACTTTTCCACTTTTTGTCTTGTCCACTAAAACCCTTGATTTTTCATCTGAATAAATGCTACTATTAGGACACATAATATTAAAAGAAACCCCCATCTATTTAGTTATTTGTTTGGTCACTTATAACTTTAACAGATGGGGTTTTTCTGTGCAACCAATTTTAAGGGTTTTCCAATACTTTAAAACACATACATACCAACACTTCAACGCACCTTTCAGCAACTAAAATAAAAATGACGTTATTTCTATATGTATCAAGATAAGAAAGAACAAGTTCAAAACCATCAAAAAAAGACACCTTTTCAGGTGCTTTTTTTATTTTATAAACTCATTCCCTGATCTCGACTTCGTTCTTTTTTTACCTCTCGGTTATGAGTTAGTTCAAATTCGTTCTTTTTAGGTTCTAAATCGTGTTTTTCTTGGAATTGTGCTGTTTTATCCTTTACCTTGTCTACAAACCCCTTAAAAACGTTTTTAAAGGCTTTTAAGCGTCTGTACGTTCCTTAAGGAATTATTCCTTAGTGCTTTCTAGGTTAATGTCATGATAATAATGGTTTCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTCCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTGTTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGCAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCTTAATAAGATGATCTTCTTGAGATCGTTTTGGTCTGCGCGTAATCTCTTGCTCTGAAAACGAAAAAACCGCCTTGCAGGGAGGTTTTTCGAAGGTTCTCTGAGCTACCAACTCTTTGAACCGAGGTAACTGGCTTGCAGGAGCGCAGTCACCAAAACTTGTCCTTTCAGTTTAGCCTTAACCGGCGCATGACTTCAAGACTAACTCCTCTAAATCAATTACCAGTGGCTGCTGCCAGTGGTGCTTTTGCATGTCTTTCCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGACTGAACGGGGGGTTCGTGCATACAGTCCAGCTTGGAGCGAACTGCCTACCCGGAACTGAGTGTCAGGCGTGGAATGAGACAAACGCGGCCATAACAGCGGAATGACACCGGTAAACCGAAAGGCAGGAACAGGAGAGCGCACGAGGGAGCCGCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCACTGATTTGAGCGTCAGATTTCGTGATGCTTGTCAGGGGGCGGAGCCTATGGAAAAACGCTTTGCCCGAGCCTATGGAAAAACGCTTTGCCCCACACAGGCTCTTGAACAAGGGATAACAATTTGTCATAGCTGTATTCGTTACAAGGAGGATTTTCGAAAAAACACCCTAACGGGTGTTTTTTTATAGCTGGTCTCCCCAAGTGCTGTAAAAAACGCCGAATGAAGCGGATGAAATTGCTCATCGTCTCGTGAAAAAGCCGAAGAAGGTTAAGCCTGGGTATAAAAAGAAAATGAGCTATGAGATGGAGAAAGCCATAACCATGAGTGATAACACTGGTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTTTTTTTCTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCCTCAATGATCTCCTTATCCGGTTAAGATGGC >pCas9g1-D15-GFP(SEQ ID No: 239)GTGACTGGGAAAACCCTGGCGACTAGTCTTGGACTCCTGTTGATAGATCCAGTAATGACCTCAGAACTCCATCTGGATTTGTTCAGAACGCTCGGTTGCCGCCGGGCGTTTTTTATTGGTGAGAATCCAGGGGTCCCCAATAATTACGATTTAAATCCTTCAAACTTCCCAAAGGCGAGCCCTAGTGACATTAGAAAACCGACTGTAAAAAGTACAGTCGGCATTATCTCATATTATAAAAGCCAGTCATTAGGCCTATCTGACAATTCCTGAATAGAGTTCATAAACAATCCTGCATGATAACCATCACAAACAGAATGATGTACCTGTAAAGATAGCGGTAAATATATTGAATTACCTTTATTAATGAATTTTCCTGCTGTAATAATGGGTAGAAGGTAATTACTATTATTATTGATATTTAAGTTAAACCCAGTAAATGAAGTCCATGGAATAATAGAAAGAGAAAAAGCATTTTCAGGTATAGGTGTTTTGGGAAACAATTTCCCCGAACCATTATATTTCTCTACATCAGAAAGGTATAAATCATAAAACTCTTTGAAGTCATTCTTTACAGGAGTCCAAATACCAGAGAATGTTTTAGATACACCATCAAAAATTGTATAAAGTGGCTCTAACTTATCCCAATAACCTAACTCTCCGTCGCTATTGTAACCAGTTCTAAAAGCTGTATTTGAGTTTATCACCCTTGTCACTAAGAAAATAAATGCAGGGTAAAATTTATATCCTTCTTGTTTTATGTTTCGGTATAAAACACTAATATCAATTTCTGTGGTTATACTAAAAGTCGTTTGTTGGTTCAAATAATGATTAAATATCTCTTTTCTCTTCCAATTGTCTAAATCAATTTTATTAAAGTTCATTTGATATGCCTCCTAAATTTTTATCTAAAGTGAATTTAGGAGGCTTACTTGTCTGCTTTCTTCATTAGAATCAATCCTTTTTTAAAAGTCAATCCCGTTTGTTGAAGACTTTTGTCCTTTTCCGCTGCATAAACAATATGGCCCGTTTGTTGAACTACTCTTTAATAAAATAATTTTTCCGTTCCCAATTCCACATTGCAATAATAGAAAATCCATCTTCATCGGCTTTTTCGTCATCATCTGTATGAATCAAATCGCCTTCTTCTGTGTCATCAAGGTTTAATTTTTTATGTATTTCTTTTAACAAACCACCATAGGAGATTAACCTTTTACGGTGTAAACCTTCCTCCAAATCAGACAAACGTTTCAAATTCTTTTCTTCATCATCGGTCATAAAATCCGTATCCTTTACAGGATATTTTGCAGTTTCGTCAATTGCCGATTGTATATCCGATTTATATTTATTTTTCGGTCGAATCATTTGAACTTTTACATTTGGATCATAGTCTAATTTCATTGCCTTTTTCCAAAATTGAATCCATTGTTTTTGATTCACGTAGTTTTCTGTATTCTTAAAATAAGTTGGTTCCACACATACCAATACATGCATGTGCTGATTATAAGAATTATCTTTATTATTTATTGTCACTTCCGTTGCACGCATAAAACCAACAAGATTTTTATTAATTTTTTTATATTGCATCATTCGGCGAAATCCTTGAGCCATATCTGACAAACTCTTATTTAATTCTTCGCCATCATAAACATTTTTAACTGTTAATGTGAGAAACAACCAACGAACTGTTGGCTTTTGTTTAATAACTTCAGCAACAACCTTTTGTGACTGAATGCCATGTTTCATTGCTCTCCTCCAGTTGCACATTGGACAAAGCCTGGATTTACAAAACCACACTCGATACAACTTTCTTTCGCCTGTTTCACGATTTTGTTTATACTCTAATATTTCAGCACAATCTTTTACTCTTTCAGCCTTTTTAAATTCAAGAATATGCAGAAGTTCAAAGTAATCAACATTAGCGATTTTCTTTTCTCTCCATGGTCTCACTTTTCCACTTTTTGTCTTGTCCACTAAAACCCTTGATTTTTCATCTGAATAAATGCTACTATTAGGACACATAATATTAAAAGAAACCCCCATCTATTTAGTTATTTGTTTGGTCACTTATAACTTTAACAGATGGGGTTTTTCTGTGCAACCAATTTTAAGGGTTTTCCAATACTTTAAAACACATACATACCAACACTTCAACGCACCTTTCAGCAACTAAAATAAAAATGACGTTATTTCTATATGTATCAAGATAAGAAAGAACAAGTTCAAAACCATCAAAAAAAGACACCTTTTCAGGTGCTTTTTTTATTTTATAAACTCATTCCCTGATCTCGACTTCGTTCTTTTTTTACCTCTCGGTTATGAGTTAGTTCAAATTCGTTCTTTTTAGGTTCTAAATCGTGTTTTTCTTGGAATTGTGCTGTTTTATCCTTTACCTTGTCTACAAACCCCTTAAAAACGTTTTTAAAGGCTTTTAAGCGTCTGTACGTTCCTTAAGGAATTATTCCTTAGTGCTTTCTAGGTTAATGTCATGATAATAATGGTTTCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTCCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTGTTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGCAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCTTAATAAGATGATCTTCTTGAGATCGTTTTGGTCTGCGCGTAATCTCTTGCTCTGAAAACGAAAAAACCGCCTTGCAGGGAGGTTTTTCGAAGGTTCTCTGAGCTACCAACTCTTTGAACCGAGGTAACTGGCTTGCAGGAGCGCAGTCACCAAAACTTGTCCTTTCAGTTTAGCCTTAACCGGCGCATGACTTCAAGACTAACTCCTCTAAATCAATTACCAGTGGCTGCTGCCAGTGGTGCTTTTGCATGTCTTTCCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGACTGAACGGGGGGTTCGTGCATACAGTCCAGCTTGGAGCGAACTGCCTACCCGGAACTGAGTGTCAGGCGTGGAATGAGACAAACGCGGCCATAACAGCGGAATGACACCGGTAAACCGAAAGGCAGGAACAGGAGAGCGCACGAGGGAGCCGCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCACTGATTTGAGCGTCAGATTTCGTGATGCTTGTCAGGGGGCGGAGCCTATGGAAAAACGCTTTGCCCGAGCCTATGGAAAAACGCTTTGCCCCACACAGGCTCTTGAACAAGGGATAACAATTTGTCATAGCTGTATTCGTTACAAGGAGGATTTTCGAAAAAACACCCTAACGGGTGTTTTTTTATAGCTGGTCTCCCCAAGTGCTGTAAAAAACGCCGAATGAAGCGGATGAAATTGCTCATCGTCTCGTGAAAAAGCCGAAGAAGGTTAAGCCTGGGTATAAAAAGAAAATGAGCTATGAGATGGAGAAAGCCATAACCATGAGTGATAACACTGGTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTTTTTTTCTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCCTCAATGATCTCCTTATCCGGTTAAGATGGCTTTTAAATCAATTTTCAGCTCCTGTATACAATTACCAAAGTTTTTCTGAATGAAGCCATGTGTTTTGACACATTCTATACTCACAAGGAGGTGAGACACATGAGTAAATCCTGGGGCAAATTCATCGAGGAGGAAGAGGCGGAAATGGCTTCCCGTCGTAATCTAATGATTGTCGATGGAACTAACTTAGGCTTTCGCTTCAAACATAACAATAGTAAAAAACCATTTGCCTCAAGTTATGTTTCAACTATTCAATCTCTGGCAAAATCCTACTCTGCCAGAACTACGATTGTTCTAGGTGATAAGGGCAAAAGCGTGTTCAGACTAGAACATCTACCAGAGTATAAAGGTAATCGTGATGAAAAGTACGCACAACGTACGGAAGAGGAGAAAGCGCTAGATGAGCAGTTCTTCGAATACCTCAAAGATGCTTTCGAGTTGTGTAAAACTACATTCCCAACTTTTACCATTCGTGGTGTAGAAGCAGATGACATGGCGGCGTATATTGTTAAGCTCATCGGGCATCTTTATGATCACGTTTGGCTAATATCTACAGATGGTGACTGGGATACTTTATTAACGGATAAAGTTTCTCGTTTTTCTTTCACAACACGTCGTGAGTATCATCTTCGTGATATGTATGAGCACCATAACGTGGACGACGTAGAACAGTTTATCTCCCTGAAAGCAATTATGGGAGATCTAGGAGATAATATTCGTGGTGTTGAAGGAATAGGAGCAAAACGCGGATATAATATTATTCGTGAGTTTGGTAACGTACTGGATATTATTGATCAGCTTCCACTGCCTGGAAAGCAGAAATATATACAGAACCTGAATGCATCGGAAGAACTGCTTTTCCGAAACTTGATTCTGGTTGATTTACCTACCTACTGTGTGGATGCTATTGCTGCTGTAGGTCAAGATGTGTTAGATAAGTTCACGAAAGACATCCTTGAGATCGCGGAACAATGATAAGCTCTTAAAGGGGGTTTTAGATACCAGAGATGGATAAGAAATACTCAATAGGCTTAGATATCGGCACAAATAGCGTCGGATGGGCGGTGATCACTGATGAATATAAGGTTCCGTCTAAAAAGTTCAAGGTTCTGGGAAATACAGACCGCCACAGTATCAAAAAAAATCTTATAGGGGCTCTTTTATTTGACAGTGGAGAGACAGCGGAAGCGACTCGTCTCAAACGGACAGCTCGTAGAAGGTATACACGTCGGAAGAATCGTATTTGTTATCTACAGGAGATTTTTTCAAATGAGATGGCGAAAGTAGATGATAGTTTCTTTCATCGACTTGAAGAGTCTTTTTTGGTGGAAGAAGACAAGAAGCATGAACGTCATCCTATTTTTGGAAATATAGTAGATGAAGTTGCTTATCATGAGAAATATCCAACTATCTATCATCTGCGAAAAAAATTGGTAGATTCTACTGATAAAGCGGATTTGCGCTTAATCTATTTGGCCTTAGCGCATATGATTAAGTTTCGTGGTCATTTTTTGATTGAGGGAGATTTAAATCCTGATAATAGTGATGTGGACAAACTATTTATCCAGTTGGTACAAACCTACAATCAATTATTTGAAGAAAACCCTATTAACGCAAGTGGAGTAGATGCTAAAGCGATTCTTTCTGCACGATTGAGTAAATCAAGACGATTAGAAAATCTCATTGCTCAGCTCCCCGGTGAGAAGAAAAATGGCTTATTTGGGAATCTCATTGCTTTGTCATTGGGTTTGACCCCTAATTTTAAATCAAATTTTGATTTGGCAGAAGATGCTAAATTACAGCTTTCAAAAGATACTTACGATGATGATTTAGATAATTTATTGGCGCAAATTGGAGATCAATATGCTGATTTGTTTTTGGCAGCTAAGAATTTATCAGATGCTATTTTACTTTCAGATATCCTAAGAGTAAATACTGAAATAACTAAGGCTCCCCTATCAGCTTCAATGATTAAACGCTACGATGAACATCATCAAGACTTGACTCTTTTAAAAGCTTTAGTTCGACAACAACTTCCAGAAAAGTATAAAGAAATCTTTTTTGATCAATCAAAAAACGGATATGCAGGTTATATTGATGGGGGAGCTAGCCAAGAAGAATTTTATAAATTTATCAAACCAATTTTAGAAAAAATGGATGGTACTGAGGAATTATTGGTGAAACTAAATCGTGAAGATTTGCTGCGCAAGCAACGGACCTTTGACAACGGCTCTATTCCCCATCAAATTCACTTGGGTGAGCTGCATGCTATTTTGAGAAGACAAGAAGACTTTTATCCATTTTTAAAAGACAATCGTGAGAAGATTGAAAAAATCTTGACTTTTCGAATTCCTTATTATGTTGGTCCATTGGCGCGTGGCAATAGTCGTTTTGCATGGATGACTCGGAAGTCTGAAGAAACAATTACCCCATGGAATTTTGAAGAAGTTGTCGATAAAGGTGCTTCAGCTCAATCATTTATTGAACGCATGACAAACTTTGATAAAAATCTTCCAAATGAAAAAGTACTACCAAAACATAGTTTGCTTTATGAGTATTTTACGGTTTATAACGAATTGACAAAGGTCAAATATGTTACTGAAGGAATGCGAAAACCAGCATTTCTTTCAGGTGAACAGAAGAAAGCCATTGTTGATTTACTCTTCAAAACAAATCGAAAAGTAACCGTTAAGCAATTAAAAGAAGATTATTTCAAAAAAATAGAATGTTTTGATAGTGTTGAAATTTCAGGAGTTGAAGATAGATTTAATGCTTCATTAGGTACCTACCATGATTTGCTAAAAATTATTAAAGATAAAGATTTTTTGGATAATGAAGAAAATGAAGATATCTTAGAGGATATTGTTTTAACATTGACCTTATTTGAAGATAGGGAGATGATTGAGGAAAGACTTAAAACATATGCTCACCTCTTTGATGATAAGGTGATGAAACAGCTTAAACGTCGCCGTTATACTGGTTGGGGACGTTTGTCTCGAAAATTGATTAATGGTATTAGGGATAAGCAATCTGGCAAAACAATATTAGATTTTTTGAAATCAGATGGTTTTGCCAATCGCAATTTTATGCAGCTGATCCATGATGATAGTTTGACATTTAAAGAAGACATTCAAAAAGCACAAGTGTCTGGACAAGGCGATAGTTTACATGAACATATTGCAAATTTAGCTGGTAGCCCTGCTATTAAAAAAGGTATTTTACAGACTGTAAAAGTTGTTGATGAATTGGTCAAAGTAATGGGGCGGCATAAGCCAGAAAATATCGTTATTGAAATGGCACGTGAAAATCAGACAACTCAAAAGGGCCAGAAAAATTCGCGAGAGCGTATGAAACGAATCGAAGAAGGTATCAAAGAATTAGGAAGTCAGATTCTTAAAGAGCATCCTGTTGAAAATACTCAATTGCAAAATGAAAAGCTCTATCTCTATTATCTCCAAAATGGAAGAGACATGTATGTGGACCAAGAATTAGATATTAATCGTTTAAGTGATTATGATGTCGATCACATTGTTCCACAAAGTTTCCTTAAAGACGATTCAATAGACAATAAGGTCTTAACGCGTTCTGATAAAAATCGTGGTAAATCGGATAACGTTCCAAGTGAAGAAGTAGTCAAAAAGATGAAAAACTATTGGAGACAACTTCTAAACGCCAAGTTAATCACTCAACGTAAGTTTGATAATTTAACGAAAGCTGAACGTGGAGGTTTGAGTGAACTTGATAAAGCTGGTTTTATCAAACGCCAATTGGTTGAAACTCGCCAAATCACTAAGCATGTGGCACAAATTTTGGATAGTCGCATGAATACTAAATACGATGAAAATGATAAACTTATTCGAGAGGTTAAAGTGATTACCTTAAAATCTAAATTAGTTTCTGACTTCCGAAAAGATTTCCAATTCTATAAAGTACGTGAGATTAACAATTACCATCATGCCCATGATGCGTATCTAAATGCCGTCGTTGGAACTGCTTTGATTAAGAAATATCCAAAACTTGAATCGGAGTTTGTCTATGGTGATTATAAAGTTTATGATGTTCGTAAAATGATTGCTAAGTCTGAGCAAGAAATAGGCAAAGCAACCGCAAAATATTTCTTTTACTCTAATATCATGAACTTCTTCAAAACAGAAATTACACTTGCAAATGGAGAGATTCGCAAACGCCCTCTAATCGAAACTAATGGGGAAACTGGAGAAATTGTCTGGGATAAAGGGCGAGATTTTGCCACAGTGCGCAAAGTATTGTCCATGCCCCAAGTCAATATTGTCAAGAAAACAGAAGTACAGACAGGCGGATTCTCCAAGGAGTCAATTTTACCAAAAAGAAATTCGGACAAGCTTATTGCTCGTAAAAAAGACTGGGATCCAAAAAAATATGGTGGTTTTGATAGTCCAACGGTAGCTTATTCAGTCCTAGTGGTTGCTAAGGTGGAAAAAGGGAAATCGAAGAAGTTAAAATCCGTTAAAGAGTTACTAGGGATCACAATTATGGAAAGAAGTTCCTTTGAAAAAAATCCGATTGACTTTTTAGAAGCTAAAGGATATAAGGAAGTTAAAAAAGACTTAATCATTAAACTACCTAAATATAGTCTTTTTGAGTTAGAAAACGGTCGTAAACGGATGCTGGCTAGTGCCGGAGAATTACAAAAAGGAAATGAGCTGGCTCTGCCAAGCAAATATGTGAATTTTTTATATTTAGCTAGTCATTATGAAAAGTTGAAGGGTAGTCCAGAAGATAACGAACAAAAACAATTGTTTGTGGAGCAGCATAAGCATTATTTAGATGAGATTATTGAGCAAATCAGTGAATTTTCTAAGCGTGTTATTTTAGCAGATGCCAATTTAGATAAAGTTCTTAGTGCATATAACAAACATAGAGACAAACCAATACGTGAACAAGCAGAAAATATTATTCATTTATTTACGTTGACGAATCTTGGAGCTCCCGCTGCTTTTAAATATTTTGATACAACAATTGATCGTAAACGATATACGTCTACAAAAGAAGTTTTAGATGCCACTCTTATCCATCAATCCATCACTGGTCTTTATGAAACACGCATTGATTTGAGTCAGCTAGGAGGTGACTGATAATCAAATGTCAGACGAAAATGCCAATTATTGAAGCGGCTAACGCCGCTTTTTTTGTTTCTGGTCTCCCTTGCTTGTACTTTACAGTATAGCTTCCTCAATGATCTCCTTATCCGGTTAAGATGGCAAGCTTGACAAGTATTTCTTCAGAATTTACAATGAAGTTTACTAGAGGATTAACTAATAAGGAGGGCAAACTACTAGAGATGTCTAAACGTCGTATGAAGTACCACAGCAACAATGAGATCAGCTATTACAATTTCCTACATAGCATGAAGGACAAAATCGTGACGGTGTATAGAGGCGGCCCTGAGAGCAAGAAGGGCAAGCTGACGGCAGTGAAGAGCGACTACATCGCGCTGCAGGCGGAGAAGAAGATCATCTACTATCAACTTGAACACGTTAAGTCAATCACGGAAGACACAAACAACTCAACAACGACGATCGAAACGGAAGAGATGTTAGACGCGGACGACTTCCACTCACTGATCGGCCACCTGATCAATCAGAGCGTGCAGTTCAATCAGGGAGGACCAGAAAGCAAGAAAGGCCGCCTTGTATGGTTAGGCGACGACTATGCGGCACTGAATACGAACGAAGACGGAGTGGTATACTTCAACATTCACCACATTAAGTCCATCTCAAAGCACGAACCGGACCTTAAGATCGAGGAACAAACACCGGTGGGCGTGCTTGAGGCGGACGACCTGTCAGAAGTGTTCAAATCATTAACGCACAAGTGGGTGAGCATCAACAGAGGCGGCCCTGAGGCAATCGAAGGCATTTTAGTGGACAACGCAGATGGACACTACACGATCGTTAAGAACCAGGAAGTATTGAGAATTTACCCGTTCCACATCAAATCAATTTCACTGGGCCCGAAGGGAAGTTATAAAAAGGAAGACCAGAAGAACGAGCAGAATCAAGAGGATAACAACGACAAAGATTCAAACAGCTTTATCAGCAGCAAAAGCTATTCAAGCAGTAAAAGCTCAAAGCGGAGCTTGAAGAGCTCTGACGACCAGAGCAGTAAGTCAGGCAGAAGTTCCAGAAGCAAGAGTAGCTCCAAGAGTAGTAAGAGGAGTTTGAAGTCCAGCGACTACCAGAGCAGTAAAAGTGGAAGAAGTTCCAGGAGCAAGTCCTCAAGTAAGTCCAGTAAGAGAAGCCTGAAGAGTAGCGACTACCAGAGCAGCAAAAGCTCAAAAAGGAGCCCGCGCAGTAGCGACTACCAGAGTAGTCGTAGCCCGGGATATAGCTCCTCCATCAAGTCTAGTGGCAAGCAGAAAGAGGACTATTCATACGAGACAATCGTTCGCACAATCGATTATCATTGGAAGAGGAAATTCGGTTTCAAACTCGGGGGGGACGGAGGTGAAATGTCTAAGGGCGAAGAGTTATTCACGGGCGTAGTTCCGATTCTTGTGGAGCTCGACGGTGATGTAAACGGGCACAAGTTTTCTGTTTCTGGGGAAGGTGAAGGCGACGCGACCTATGGGAAACTCACTCTTAAGTTCATCTGCACCACGGGGAAGTTACCAGTCCCGTGGCCAACACTGGTGACTACCTTCGCATACGGACTGCAGTGTTTTGCGCGTTATCCTGATCACATGAAACAACACGATTTTTTCAAGAGCGCCATGCCAGAAGGGTACGTCCAAGAACGCACGATTTTTTTCAAAGATGATGGGAATTACAAAACGCGTGCAGAAGTAAAATTTGAGGGCGACACCCTGGTAAACCGTATTGAACTCAAAGGAATCGACTTTAAGGAGGACGGAAACATTCTGGGCCACAAACTGGAATATAACTACAACTCACATAACGTTTATATAATGGCTGATAAGCAAAAAAATGGTATCAAGGTGAACTTTAAGATAAGACATAACATTGAGGACGGCAGTGTCCAACTTGCAGACCATTACCAGCAGAACACACCAATTGGCGACGGTCCAGTACTTTTACCGGACAACCACTATCTCTCAACTCAGAGTGCTCTGTCAAAGGACCCTAATGAAAAACGCGACCACATGGTACTGCTCGAGTTTGTGACTGCGGCCGGAATCACCCACGGGATGGACGAGCTTTACAAGTAATCAAATGTCAGACGAAAATGCCAATTATTGAAGCGGCTAACGCCGCTTTTTTTGTTTCTGGTCTCCCAACTTTGCTAAAGAGCGTCTCAGCTTCTAGAG >pCas9g2-D15-GFP (SEQ ID No: 240)TAGAGATCTGCAGTGACTGGAGCTTCTAGAGATCAGGTCAGACGCGATTTCCTGGGTGCTCGAGCCATGGGAAAGCGGTGGTGGAAAAAACGCCGAATGAAGCGGATGAAATTGCTCATCGTCTCGTGAAAAAGCCGAAGAAGGTTAAGCCTGGGTATAAAAAGAAAATGAGCTATGAGATGGAGAAATTGAAGTCATGCGCCGGTTAGTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTTTTTTTCTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCCTCAATGATCCGACAGGAAGTGGTATTAGCGACTCCTACAAGGAATAGGTGTCTGGGTCATGCAGTGACTGGGAAAACCCTGGCGACTAGTCTTGGACTCCTGTTGATAGATCCAGTAATGACCTCAGAACTCCATCTGGATTTGTTCAGAACGCTCGGTTGCCGCCGGGCGTTTTTTATTGGTGAGAATCCAGGGGTCCCCAATAATTACGATTTAAATCCTTCAAACTTCCCAAAGGCGAGCCCTAGTGACATTAGAAAACCGACTGTAAAAAGTACAGTCGGCATTATCTCATATTATAAAAGCCAGTCATTAGGCCTATCTGACAATTCCTGAATAGAGTTCATAAACAATCCTGCATGATAACCATCACAAACAGAATGATGTACCTGTAAAGATAGCGGTAAATATATTGAATTACCTTTATTAATGAATTTTCCTGCTGTAATAATGGGTAGAAGGTAATTACTATTATTATTGATATTTAAGTTAAACCCAGTAAATGAAGTCCATGGAATAATAGAAAGAGAAAAAGCATTTTCAGGTATAGGTGTTTTGGGAAACAATTTCCCCGAACCATTATATTTCTCTACATCAGAAAGGTATAAATCATAAAACTCTTTGAAGTCATTCTTTACAGGAGTCCAAATACCAGAGAATGTTTTAGATACACCATCAAAAATTGTATAAAGTGGCTCTAACTTATCCCAATAACCTAACTCTCCGTCGCTATTGTAACCAGTTCTAAAAGCTGTATTTGAGTTTATCACCCTTGTCACTAAGAAAATAAATGCAGGGTAAAATTTATATCCTTCTTGTTTTATGTTTCGGTATAAAACACTAATATCAATTTCTGTGGTTATACTAAAAGTCGTTTGTTGGTTCAAATAATGATTAAATATCTCTTTTCTCTTCCAATTGTCTAAATCAATTTTATTAAAGTTCATTTGATATGCCTCCTAAATTTTTATCTAAAGTGAATTTAGGAGGCTTACTTGTCTGCTTTCTTCATTAGAATCAATCCTTTTTTAAAAGTCAATCCCGTTTGTTGAAGACTTTTGTCCTTTTCCGCTGCATAAACAATATGGCCCGTTTGTTGAACTACTCTTTAATAAAATAATTTTTCCGTTCCCAATTCCACATTGCAATAATAGAAAATCCATCTTCATCGGCTTTTTCGTCATCATCTGTATGAATCAAATCGCCTTCTTCTGTGTCATCAAGGTTTAATTTTTTATGTATTTCTTTTAACAAACCACCATAGGAGATTAACCTTTTACGGTGTAAACCTTCCTCCAAATCAGACAAACGTTTCAAATTCTTTTCTTCATCATCGGTCATAAAATCCGTATCCTTTACAGGATATTTTGCAGTTTCGTCAATTGCCGATTGTATATCCGATTTATATTTATTTTTCGGTCGAATCATTTGAACTTTTACATTTGGATCATAGTCTAATTTCATTGCCTTTTTCCAAAATTGAATCCATTGTTTTTGATTCACGTAGTTTTCTGTATTCTTAAAATAAGTTGGTTCCACACATACCAATACATGCATGTGCTGATTATAAGAATTATCTTTATTATTTATTGTCACTTCCGTTGCACGCATAAAACCAACAAGATTTTTATTAATTTTTTTATATTGCATCATTCGGCGAAATCCTTGAGCCATATCTGACAAACTCTTATTTAATTCTTCGCCATCATAAACATTTTTAACTGTTAATGTGAGAAACAACCAACGAACTGTTGGCTTTTGTTTAATAACTTCAGCAACAACCTTTTGTGACTGAATGCCATGTTTCATTGCTCTCCTCCAGTTGCACATTGGACAAAGCCTGGATTTACAAAACCACACTCGATACAACTTTCTTTCGCCTGTTTCACGATTTTGTTTATACTCTAATATTTCAGCACAATCTTTTACTCTTTCAGCCTTTTTAAATTCAAGAATATGCAGAAGTTCAAAGTAATCAACATTAGCGATTTTCTTTTCTCTCCATGGTCTCACTTTTCCACTTTTTGTCTTGTCCACTAAAACCCTTGATTTTTCATCTGAATAAATGCTACTATTAGGACACATAATATTAAAAGAAACCCCCATCTATTTAGTTATTTGTTTGGTCACTTATAACTTTAACAGATGGGGTTTTTCTGTGCAACCAATTTTAAGGGTTTTCCAATACTTTAAAACACATACATACCAACACTTCAACGCACCTTTCAGCAACTAAAATAAAAATGACGTTATTTCTATATGTATCAAGATAAGAAAGAACAAGTTCAAAACCATCAAAAAAAGACACCTTTTCAGGTGCTTTTTTTATTTTATAAACTCATTCCCTGATCTCGACTTCGTTCTTTTTTTACCTCTCGGTTATGAGTTAGTTCAAATTCGTTCTTTTTAGGTTCTAAATCGTGTTTTTCTTGGAATTGTGCTGTTTTATCCTTTACCTTGTCTACAAACCCCTTAAAAACGTTTTTAAAGGCTTTTAAGCGTCTGTACGTTCCTTAAGGAATTATTCCTTAGTGCTTTCTAGGTTAATGTCATGATAATAATGGTTTCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTCCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTGTTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGCAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCTTAATAAGATGATCTTCTTGAGATCGTTTTGGTCTGCGCGTAATCTCTTGCTCTGAAAACGAAAAAACCGCCTTGCAGGGAGGTTTTTCGAAGGTTCTCTGAGCTACCAACTCTTTGAACCGAGGTAACTGGCTTGCAGGAGCGCAGTCACCAAAACTTGTCCTTTCAGTTTAGCCTTAACCGGCGCATGACTTCAAGACTAACTCCTCTAAATCAATTACCAGTGGCTGCTGCCAGTGGTGCTTTTGCATGTCTTTCCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGACTGAACGGGGGGTTCGTGCATACAGTCCAGCTTGGAGCGAACTGCCTACCCGGAACTGAGTGTCAGGCGTGGAATGAGACAAACGCGGCCATAACAGCGGAATGACACCGGTAAACCGAAAGGCAGGAACAGGAGAGCGCACGAGGGAGCCGCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCACTGATTTGAGCGTCAGATTTCGTGATGCTTGTCAGGGGGCGGAGCCTATGGAAAAACGCTTTGCCCGAGCCTATGGAAAAACGCTTTGCCCCACACAGGCTCTTGAACAAGGGATAACAATTTGTCATAGCTGTATTCGTTACAAGGAGGATTTTCGAAAAAACACCCTAACGGGTGTTTTTTTATAGCTGGTCTCCCCAAGTGCTGTAAAAAACGCCGAATGAAGCGGATGAAATTGCTCATCGTCTCGTGAAAAAGCCGAAGAAGGTTAAGCCTGGGTATAAAAAGAAAATGAGCTATGAGATGGAGAAAGCCATAACCATGAGTGATAACACTGGTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTTTTTTTCTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCCTCAATGATCTCCTTATCCGGTTAAGATGGCTTTTAAATCAATTTTCAGCTCCTGTATACAATTACCAAAGTTTTTCTGAATGAAGCCATGTGTTTTGACACATTCTATACTCACAAGGAGGTGAGACACATGAGTAAATCCTGGGGCAAATTCATCGAGGAGGAAGAGGCGGAAATGGCTTCCCGTCGTAATCTAATGATTGTCGATGGAACTAACTTAGGCTTTCGCTTCAAACATAACAATAGTAAAAAACCATTTGCCTCAAGTTATGTTTCAACTATTCAATCTCTGGCAAAATCCTACTCTGCCAGAACTACGATTGTTCTAGGTGATAAGGGCAAAAGCGTGTTCAGACTAGAACATCTACCAGAGTATAAAGGTAATCGTGATGAAAAGTACGCACAACGTACGGAAGAGGAGAAAGCGCTAGATGAGCAGTTCTTCGAATACCTCAAAGATGCTTTCGAGTTGTGTAAAACTACATTCCCAACTTTTACCATTCGTGGTGTAGAAGCAGATGACATGGCGGCGTATATTGTTAAGCTCATCGGGCATCTTTATGATCACGTTTGGCTAATATCTACAGATGGTGACTGGGATACTTTATTAACGGATAAAGTTTCTCGTTTTTCTTTCACAACACGTCGTGAGTATCATCTTCGTGATATGTATGAGCACCATAACGTGGACGACGTAGAACAGTTTATCTCCCTGAAAGCAATTATGGGAGATCTAGGAGATAATATTCGTGGTGTTGAAGGAATAGGAGCAAAACGCGGATATAATATTATTCGTGAGTTTGGTAACGTACTGGATATTATTGATCAGCTTCCACTGCCTGGAAAGCAGAAATATATACAGAACCTGAATGCATCGGAAGAACTGCTTTTCCGAAACTTGATTCTGGTTGATTTACCTACCTACTGTGTGGATGCTATTGCTGCTGTAGGTCAAGATGTGTTAGATAAGTTCACGAAAGACATCCTTGAGATCGCGGAACAATGATAAGCTCTTAAAGGGGGTTTTAGATACCAGAGATGGATAAGAAATACTCAATAGGCTTAGATATCGGCACAAATAGCGTCGGATGGGCGGTGATCACTGATGAATATAAGGTTCCGTCTAAAAAGTTCAAGGTTCTGGGAAATACAGACCGCCACAGTATCAAAAAAAATCTTATAGGGGCTCTTTTATTTGACAGTGGAGAGACAGCGGAAGCGACTCGTCTCAAACGGACAGCTCGTAGAAGGTATACACGTCGGAAGAATCGTATTTGTTATCTACAGGAGATTTTTTCAAATGAGATGGCGAAAGTAGATGATAGTTTCTTTCATCGACTTGAAGAGTCTTTTTTGGTGGAAGAAGACAAGAAGCATGAACGTCATCCTATTTTTGGAAATATAGTAGATGAAGTTGCTTATCATGAGAAATATCCAACTATCTATCATCTGCGAAAAAAATTGGTAGATTCTACTGATAAAGCGGATTTGCGCTTAATCTATTTGGCCTTAGCGCATATGATTAAGTTTCGTGGTCATTTTTTGATTGAGGGAGATTTAAATCCTGATAATAGTGATGTGGACAAACTATTTATCCAGTTGGTACAAACCTACAATCAATTATTTGAAGAAAACCCTATTAACGCAAGTGGAGTAGATGCTAAAGCGATTCTTTCTGCACGATTGAGTAAATCAAGACGATTAGAAAATCTCATTGCTCAGCTCCCCGGTGAGAAGAAAAATGGCTTATTTGGGAATCTCATTGCTTTGTCATTGGGTTTGACCCCTAATTTTAAATCAAATTTTGATTTGGCAGAAGATGCTAAATTACAGCTTTCAAAAGATACTTACGATGATGATTTAGATAATTTATTGGCGCAAATTGGAGATCAATATGCTGATTTGTTTTTGGCAGCTAAGAATTTATCAGATGCTATTTTACTTTCAGATATCCTAAGAGTAAATACTGAAATAACTAAGGCTCCCCTATCAGCTTCAATGATTAAACGCTACGATGAACATCATCAAGACTTGACTCTTTTAAAAGCTTTAGTTCGACAACAACTTCCAGAAAAGTATAAAGAAATCTTTTTTGATCAATCAAAAAACGGATATGCAGGTTATATTGATGGGGGAGCTAGCCAAGAAGAATTTTATAAATTTATCAAACCAATTTTAGAAAAAATGGATGGTACTGAGGAATTATTGGTGAAACTAAATCGTGAAGATTTGCTGCGCAAGCAACGGACCTTTGACAACGGCTCTATTCCCCATCAAATTCACTTGGGTGAGCTGCATGCTATTTTGAGAAGACAAGAAGACTTTTATCCATTTTTAAAAGACAATCGTGAGAAGATTGAAAAAATCTTGACTTTTCGAATTCCTTATTATGTTGGTCCATTGGCGCGTGGCAATAGTCGTTTTGCATGGATGACTCGGAAGTCTGAAGAAACAATTACCCCATGGAATTTTGAAGAAGTTGTCGATAAAGGTGCTTCAGCTCAATCATTTATTGAACGCATGACAAACTTTGATAAAAATCTTCCAAATGAAAAAGTACTACCAAAACATAGTTTGCTTTATGAGTATTTTACGGTTTATAACGAATTGACAAAGGTCAAATATGTTACTGAAGGAATGCGAAAACCAGCATTTCTTTCAGGTGAACAGAAGAAAGCCATTGTTGATTTACTCTTCAAAACAAATCGAAAAGTAACCGTTAAGCAATTAAAAGAAGATTATTTCAAAAAAATAGAATGTTTTGATAGTGTTGAAATTTCAGGAGTTGAAGATAGATTTAATGCTTCATTAGGTACCTACCATGATTTGCTAAAAATTATTAAAGATAAAGATTTTTTGGATAATGAAGAAAATGAAGATATCTTAGAGGATATTGTTTTAACATTGACCTTATTTGAAGATAGGGAGATGATTGAGGAAAGACTTAAAACATATGCTCACCTCTTTGATGATAAGGTGATGAAACAGCTTAAACGTCGCCGTTATACTGGTTGGGGACGTTTGTCTCGAAAATTGATTAATGGTATTAGGGATAAGCAATCTGGCAAAACAATATTAGATTTTTTGAAATCAGATGGTTTTGCCAATCGCAATTTTATGCAGCTGATCCATGATGATAGTTTGACATTTAAAGAAGACATTCAAAAAGCACAAGTGTCTGGACAAGGCGATAGTTTACATGAACATATTGCAAATTTAGCTGGTAGCCCTGCTATTAAAAAAGGTATTTTACAGACTGTAAAAGTTGTTGATGAATTGGTCAAAGTAATGGGGCGGCATAAGCCAGAAAATATCGTTATTGAAATGGCACGTGAAAATCAGACAACTCAAAAGGGCCAGAAAAATTCGCGAGAGCGTATGAAACGAATCGAAGAAGGTATCAAAGAATTAGGAAGTCAGATTCTTAAAGAGCATCCTGTTGAAAATACTCAATTGCAAAATGAAAAGCTCTATCTCTATTATCTCCAAAATGGAAGAGACATGTATGTGGACCAAGAATTAGATATTAATCGTTTAAGTGATTATGATGTCGATCACATTGTTCCACAAAGTTTCCTTAAAGACGATTCAATAGACAATAAGGTCTTAACGCGTTCTGATAAAAATCGTGGTAAATCGGATAACGTTCCAAGTGAAGAAGTAGTCAAAAAGATGAAAAACTATTGGAGACAACTTCTAAACGCCAAGTTAATCACTCAACGTAAGTTTGATAATTTAACGAAAGCTGAACGTGGAGGTTTGAGTGAACTTGATAAAGCTGGTTTTATCAAACGCCAATTGGTTGAAACTCGCCAAATCACTAAGCATGTGGCACAAATTTTGGATAGTCGCATGAATACTAAATACGATGAAAATGATAAACTTATTCGAGAGGTTAAAGTGATTACCTTAAAATCTAAATTAGTTTCTGACTTCCGAAAAGATTTCCAATTCTATAAAGTACGTGAGATTAACAATTACCATCATGCCCATGATGCGTATCTAAATGCCGTCGTTGGAACTGCTTTGATTAAGAAATATCCAAAACTTGAATCGGAGTTTGTCTATGGTGATTATAAAGTTTATGATGTTCGTAAAATGATTGCTAAGTCTGAGCAAGAAATAGGCAAAGCAACCGCAAAATATTTCTTTTACTCTAATATCATGAACTTCTTCAAAACAGAAATTACACTTGCAAATGGAGAGATTCGCAAACGCCCTCTAATCGAAACTAATGGGGAAACTGGAGAAATTGTCTGGGATAAAGGGCGAGATTTTGCCACAGTGCGCAAAGTATTGTCCATGCCCCAAGTCAATATTGTCAAGAAAACAGAAGTACAGACAGGCGGATTCTCCAAGGAGTCAATTTTACCAAAAAGAAATTCGGACAAGCTTATTGCTCGTAAAAAAGACTGGGATCCAAAAAAATATGGTGGTTTTGATAGTCCAACGGTAGCTTATTCAGTCCTAGTGGTTGCTAAGGTGGAAAAAGGGAAATCGAAGAAGTTAAAATCCGTTAAAGAGTTACTAGGGATCACAATTATGGAAAGAAGTTCCTTTGAAAAAAATCCGATTGACTTTTTAGAAGCTAAAGGATATAAGGAAGTTAAAAAAGACTTAATCATTAAACTACCTAAATATAGTCTTTTTGAGTTAGAAAACGGTCGTAAACGGATGCTGGCTAGTGCCGGAGAATTACAAAAAGGAAATGAGCTGGCTCTGCCAAGCAAATATGTGAATTTTTTATATTTAGCTAGTCATTATGAAAAGTTGAAGGGTAGTCCAGAAGATAACGAACAAAAACAATTGTTTGTGGAGCAGCATAAGCATTATTTAGATGAGATTATTGAGCAAATCAGTGAATTTTCTAAGCGTGTTATTTTAGCAGATGCCAATTTAGATAAAGTTCTTAGTGCATATAACAAACATAGAGACAAACCAATACGTGAACAAGCAGAAAATATTATTCATTTATTTACGTTGACGAATCTTGGAGCTCCCGCTGCTTTTAAATATTTTGATACAACAATTGATCGTAAACGATATACGTCTACAAAAGAAGTTTTAGATGCCACTCTTATCCATCAATCCATCACTGGTCTTTATGAAACACGCATTGATTTGAGTCAGCTAGGAGGTGACTGATAATCAAATGTCAGACGAAAATGCCAATTATTGAAGCGGCTAACGCCGCTTTTTTTGTTTCTGGTCTCCCTTGCTTGTACTTTACAGTATAGCTTCCTCAATGATCTCCTTATCCGGTTAAGATGGCAAGCTTGACAAGTATTTCTTCAGAATTTACAATGAAGTTTACTAGAGGATTAACTAATAAGGAGGGCAAACTACTAGAGATGTCTAAACGTCGTATGAAGTACCACAGCAACAATGAGATCAGCTATTACAATTTCCTACATAGCATGAAGGACAAAATCGTGACGGTGTATAGAGGCGGCCCTGAGAGCAAGAAGGGCAAGCTGACGGCAGTGAAGAGCGACTACATCGCGCTGCAGGCGGAGAAGAAGATCATCTACTATCAACTTGAACACGTTAAGTCAATCACGGAAGACACAAACAACTCAACAACGACGATCGAAACGGAAGAGATGTTAGACGCGGACGACTTCCACTCACTGATCGGCCACCTGATCAATCAGAGCGTGCAGTTCAATCAGGGAGGACCAGAAAGCAAGAAAGGCCGCCTTGTATGGTTAGGCGACGACTATGCGGCACTGAATACGAACGAAGACGGAGTGGTATACTTCAACATTCACCACATTAAGTCCATCTCAAAGCACGAACCGGACCTTAAGATCGAGGAACAAACACCGGTGGGCGTGCTTGAGGCGGACGACCTGTCAGAAGTGTTCAAATCATTAACGCACAAGTGGGTGAGCATCAACAGAGGCGGCCCTGAGGCAATCGAAGGCATTTTAGTGGACAACGCAGATGGACACTACACGATCGTTAAGAACCAGGAAGTATTGAGAATTTACCCGTTCCACATCAAATCAATTTCACTGGGCCCGAAGGGAAGTTATAAAAAGGAAGACCAGAAGAACGAGCAGAATCAAGAGGATAACAACGACAAAGATTCAAACAGCTTTATCAGCAGCAAAAGCTATTCAAGCAGTAAAAGCTCAAAGCGGAGCTTGAAGAGCTCTGACGACCAGAGCAGTAAGTCAGGCAGAAGTTCCAGAAGCAAGAGTAGCTCCAAGAGTAGTAAGAGGAGTTTGAAGTCCAGCGACTACCAGAGCAGTAAAAGTGGAAGAAGTTCCAGGAGCAAGTCCTCAAGTAAGTCCAGTAAGAGAAGCCTGAAGAGTAGCGACTACCAGAGCAGCAAAAGCTCAAAAAGGAGCCCGCGCAGTAGCGACTACCAGAGTAGTCGTAGCCCGGGATATAGCTCCTCCATCAAGTCTAGTGGCAAGCAGAAAGAGGACTATTCATACGAGACAATCGTTCGCACAATCGATTATCATTGGAAGAGGAAATTCGGTTTCAAACTCGGGGGGGACGGAGGTGAAATGTCTAAGGGCGAAGAGTTATTCACGGGCGTAGTTCCGATTCTTGTGGAGCTCGACGGTGATGTAAACGGGCACAAGTTTTCTGTTTCTGGGGAAGGTGAAGGCGACGCGACCTATGGGAAACTCACTCTTAAGTTCATCTGCACCACGGGGAAGTTACCAGTCCCGTGGCCAACACTGGTGACTACCTTCGCATACGGACTGCAGTGTTTTGCGCGTTATCCTGATCACATGAAACAACACGATTTTTTCAAGAGCGCCATGCCAGAAGGGTACGTCCAAGAACGCACGATTTTTTTCAAAGATGATGGGAATTACAAAACGCGTGCAGAAGTAAAATTTGAGGGCGACACCCTGGTAAACCGTATTGAACTCAAAGGAATCGACTTTAAGGAGGACGGAAACATTCTGGGCCACAAACTGGAATATAACTACAACTCACATAACGTTTATATAATGGCTGATAAGCAAAAAAATGGTATCAAGGTGAACTTTAAGATAAGACATAACATTGAGGACGGCAGTGTCCAACTTGCAGACCATTACCAGCAGAACACACCAATTGGCGACGGTCCAGTACTTTTACCGGACAACCACTATCTCTCAACTCAGAGTGCTCTGTCAAAGGACCCTAATGAAAAACGCGACCACATGGTACTGCTCGAGTTTGTGACTGCGGCCGGAATCACCCACGGGATGGACGAGCTTTACAAGTAATCAAATGTCAGACGAAAATGCCAATTATTGAAGCGGCTAACGCCGCTTTTTTTGTTTCTGGTCTCCCAACTTTGCTAAAGAGCGTCTCAGCTTCTAGAG >pCas9g1-D15-KinA(SEQ ID No: 241)ttaagatggcaagcttgacagccgaattcggattcccgcgTATATCTTGAATTAAAATTAAAATCTGCCAAGATCGAAAAATAAAAAGGATTTTTTGTGTCATTGGCGAATTATGATCTATTGAAGCAACCGTTAAGCTTACATAAGGAGGAACTACTATGGAACAGGATACGCAGCATGTTAAACCACTTCAAACAAAAACCGATATTCATGCAGTCTTGGCCTCTAATGGACGCATCATTTATATATCTGCCAACTCCAAACTGCATTTGGGCTATCTCCAAGGAGAGATGATCGGATCATTCCTCAAAACGTTTCTGCATGAGGAAGACCAATTTTTGGTTGAAAGCTATTTTTATAATGAACATCATCTGATGCCGTGCACCTTTCGTTTTATTAAAAAAGATCATACGATTGTGTGGGTGGAGGCTGCGGTAGAAATTGTTACGACAAGAGCTGAGCGGACAGAACGGGAAATCATTTTGAAAATGAAGGTTCTTGAAGAAGAAACAGGCCATCAATCCCTAAACTGCGAAAAACATGAAATCGAACCTGCAAGCCCGGAATCGACTACATATATAACGGATGATTATGAACGGTTGGTTGAAAATCTCCCGAGTCCGCTATGCATCAGTGTCAAAGGCAAGATCGTCTATGTAAACAGCGCGATGCTTTCAATGCTGGGAGCCAAAAGCAAGGATGCTATTATTGGTAAATCGTCCTATGAATTTATTGAAGAAGAATATCATGATATCGTGAAAAACAGGATTATACGAATGCAAAAAGGAATGGAAGTCGGAATGATTGAACAGACGTGGAAAAGGCTTGATGGCACACCTGTTCATTTAGAAGTGAAAGCATCCCCGACCGTCTACAAAAACCAGCAGGCTGAGCTGCTGCTGCTGATCGATATCTCTTCAAGGAAAAAATTCCAAACCATCCTGCAAAAAAGCCGTGAACGATATCAGCTGCTGATTCAAAATTCCATTGATACCATTGCGGTGATTCACAATGGAAAATGGGTATTTATGAATGAATCGGGAATTTCCCTGTTTGAAGCGGCTACATATGAGGATTTAATTGGCAAAAACATATACGATCAGCTGCATCCTTGCGATCACGAGGATGTAAAAGAGAGAATCCAAAACATTGCCGAGCAAAAAACAGAATCTGAAATTGTCAAGCAATCCTGGTTCACCTTTCAGAACAGGGTCATCTATACGGAGATGGTCTGCATTCCGACGACCTTTTTTGGTGAAGCGGCCGTCCAGGTCATTCTTCGGGACATCTCAGAGAGAAAACAAACAGAAGAATTGATGCTGAAATCGGAAAAATTATCAATCGCAGGGCAGCTCGCGGCGGGAATCGCCCATGAGATCCGCAACCCTCTTACAGCGATCAAAGGATTTTTACAGCTGATGAAACCGACAATGGAAGGCAACGAACATTACTTTGATATTGTGTTTTCTGAACTCAGCCGTATCGAATTAATACTCAGTGAACTGCTCATGCTGGCGAAACCTCAGCAAAATGCTGTCAAAGAATATTTGAACTTGAAAAAATTAATTGGTGAGGTTTCAGCCCTGTTAGAAACGCAGGCGAATTTAAATGGCATTTTTATCAGAACAAGTTATGAAAAAGACAGCATTTATATAAACGGGGATCAAAACCAATTAAAGCAGGTATTCATTAATTTAATCAAAAATGCAGTTGAATCAATGCCTGATGGGGGAACAGTAGACATTATCATAACCGAAGATGAGCATTCTGTTCATGTTACTGTCAAAGACGAAGGGGAAGGTATACCTGAAAAGGTACTAAACCGGATTGGAGAGCCATTTTTAACAACAAAAGAAAAAGGTACGGGGCTTGGATTAATGGTGACATTTAATATCATTGAAAACCATCAGGGAGTTATACATGTGGACAGCCATCCTGAAAAAGGCACAGCGTTTAAAATTTCATTTCcaaaaaaataagcatgcccggggatggacgagctttacaaGTAATCAAATGTCAGACGAAAATGCCAATTATTGAAGCGGCTAACGCCGCTTTTTTTGTTTCTGGTCTCCCAACTTTGCTAAAGAGCGTCTCAGCTTCTAGAGGTGACTGGGAAAACCCTGGCGACTAGTCTTGGACTCCTGTTGATAGATCCAGTAATGACCTCAGAACTCCATCTGGATTTGTTCAGAACGCTCGGTTGCCGCCGGGCGTTTTTTATTGGTGAGAATCCAGGGGTCCCCAATAATTACGATTTAAATCCTTCAAACTTCCCAAAGGCGAGCCCTAGTGACATTAGAAAACCGACTGTAAAAAGTACAGTCGGCATTATCTCATATTATAAAAGCCAGTCATTAGGCCTATCTGACAATTCCTGAATAGAGTTCATAAACAATCCTGCATGATAACCATCACAAACAGAATGATGTACCTGTAAAGATAGCGGTAAATATATTGAATTACCTTTATTAATGAATTTTCCTGCTGTAATAATGGGTAGAAGGTAATTACTATTATTATTGATATTTAAGTTAAACCCAGTAAATGAAGTCCATGGAATAATAGAAAGAGAAAAAGCATTTTCAGGTATAGGTGTTTTGGGAAACAATTTCCCCGAACCATTATATTTCTCTACATCAGAAAGGTATAAATCATAAAACTCTTTGAAGTCATTCTTTACAGGAGTCCAAATACCAGAGAATGTTTTAGATACACCATCAAAAATTGTATAAAGTGGCTCTAACTTATCCCAATAACCTAACTCTCCGTCGCTATTGTAACCAGTTCTAAAAGCTGTATTTGAGTTTATCACCCTTGTCACTAAGAAAATAAATGCAGGGTAAAATTTATATCCTTCTTGTTTTATGTTTCGGTATAAAACACTAATATCAATTTCTGTGGTTATACTAAAAGTCGTTTGTTGGTTCAAATAATGATTAAATATCTCTTTTCTCTTCCAATTGTCTAAATCAATTTTATTAAAGTTCATTTGATATGCCTCCTAAATTTTTATCTAAAGTGAATTTAGGAGGCTTACTTGTCTGCTTTCTTCATTAGAATCAATCCTTTTTTAAAAGTCAATCCCGTTTGTTGAAGACTTTTGTCCTTTTCCGCTGCATAAACAATATGGCCCGTTTGTTGAACTACTCTTTAATAAAATAATTTTTCCGTTCCCAATTCCACATTGCAATAATAGAAAATCCATCTTCATCGGCTTTTTCGTCATCATCTGTATGAATCAAATCGCCTTCTTCTGTGTCATCAAGGTTTAATTTTTTATGTATTTCTTTTAACAAACCACCATAGGAGATTAACCTTTTACGGTGTAAACCTTCCTCCAAATCAGACAAACGTTTCAAATTCTTTTCTTCATCATCGGTCATAAAATCCGTATCCTTTACAGGATATTTTGCAGTTTCGTCAATTGCCGATTGTATATCCGATTTATATTTATTTTTCGGTCGAATCATTTGAACTTTTACATTTGGATCATAGTCTAATTTCATTGCCTTTTTCCAAAATTGAATCCATTGTTTTTGATTCACGTAGTTTTCTGTATTCTTAAAATAAGTTGGTTCCACACATACCAATACATGCATGTGCTGATTATAAGAATTATCTTTATTATTTATTGTCACTTCCGTTGCACGCATAAAACCAACAAGATTTTTATTAATTTTTTTATATTGCATCATTCGGCGAAATCCTTGAGCCATATCTGACAAACTCTTATTTAATTCTTCGCCATCATAAACATTTTTAACTGTTAATGTGAGAAACAACCAACGAACTGTTGGCTTTTGTTTAATAACTTCAGCAACAACCTTTTGTGACTGAATGCCATGTTTCATTGCTCTCCTCCAGTTGCACATTGGACAAAGCCTGGATTTACAAAACCACACTCGATACAACTTTCTTTCGCCTGTTTCACGATTTTGTTTATACTCTAATATTTCAGCACAATCTTTTACTCTTTCAGCCTTTTTAAATTCAAGAATATGCAGAAGTTCAAAGTAATCAACATTAGCGATTTTCTTTTCTCTCCATGGTCTCACTTTTCCACTTTTTGTCTTGTCCACTAAAACCCTTGATTTTTCATCTGAATAAATGCTACTATTAGGACACATAATATTAAAAGAAACCCCCATCTATTTAGTTATTTGTTTGGTCACTTATAACTTTAACAGATGGGGTTTTTCTGTGCAACCAATTTTAAGGGTTTTCCAATACTTTAAAACACATACATACCAACACTTCAACGCACCTTTCAGCAACTAAAATAAAAATGACGTTATTTCTATATGTATCAAGATAAGAAAGAACAAGTTCAAAACCATCAAAAAAAGACACCTTTTCAGGTGCTTTTTTTATTTTATAAACTCATTCCCTGATCTCGACTTCGTTCTTTTTTTACCTCTCGGTTATGAGTTAGTTCAAATTCGTTCTTTTTAGGTTCTAAATCGTGTTTTTCTTGGAATTGTGCTGTTTTATCCTTTACCTTGTCTACAAACCCCTTAAAAACGTTTTTAAAGGCTTTTAAGCGTCTGTACGTTCCTTAAGGAATTATTCCTTAGTGCTTTCTAGGTTAATGTCATGATAATAATGGTTTCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTCCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTGTTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGCAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCTTAATAAGATGATCTTCTTGAGATCGTTTTGGTCTGCGCGTAATCTCTTGCTCTGAAAACGAAAAAACCGCCTTGCAGGGAGGTTTTTCGAAGGTTCTCTGAGCTACCAACTCTTTGAACCGAGGTAACTGGCTTGCAGGAGCGCAGTCACCAAAACTTGTCCTTTCAGTTTAGCCTTAACCGGCGCATGACTTCAAGACTAACTCCTCTAAATCAATTACCAGTGGCTGCTGCCAGTGGTGCTTTTGCATGTCTTTCCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGACTGAACGGGGGGTTCGTGCATACAGTCCAGCTTGGAGCGAACTGCCTACCCGGAACTGAGTGTCAGGCGTGGAATGAGACAAACGCGGCCATAACAGCGGAATGACACCGGTAAACCGAAAGGCAGGAACAGGAGAGCGCACGAGGGAGCCGCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCACTGATTTGAGCGTCAGATTTCGTGATGCTTGTCAGGGGGCGGAGCCTATGGAAAAACGCTTTGCCCGAGCCTATGGAAAAACGCTTTGCCCCACACAGGCTCTTGAACAAGGGATAACAATTTGTCATAGCTGTATTCGTTACAAGGAGGATTTTCGAAAAAACACCCTAACGGGTGTTTTTTTATAGCTGGTCTCCCCAAGTGCTGTAAAAAACGCCGAATGAAGCGGATGAAATTGCTCATCGTCTCGTGAAAAAGCCGAAGAAGGTTAAGCCTGGGTATAAAAAGAAAATGAGCTATGAGATGGAGAAAGCCATAACCATGAGTGATAACACTGGTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTTTTTTTCTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCCTCAATGATCTCCTTATCCGGTTAAGATGGCTTTTAAATCAATTTTCAGCTCCTGTATACAATTACCAAAGTTTTTCTGAATGAAGCCATGTGTTTTGACACATTCTATACTCACAAGGAGGTGAGACACATGAGTAAATCCTGGGGCAAATTCATCGAGGAGGAAGAGGCGGAAATGGCTTCCCGTCGTAATCTAATGATTGTCGATGGAACTAACTTAGGCTTTCGCTTCAAACATAACAATAGTAAAAAACCATTTGCCTCAAGTTATGTTTCAACTATTCAATCTCTGGCAAAATCCTACTCTGCCAGAACTACGATTGTTCTAGGTGATAAGGGCAAAAGCGTGTTCAGACTAGAACATCTACCAGAGTATAAAGGTAATCGTGATGAAAAGTACGCACAACGTACGGAAGAGGAGAAAGCGCTAGATGAGCAGTTCTTCGAATACCTCAAAGATGCTTTCGAGTTGTGTAAAACTACATTCCCAACTTTTACCATTCGTGGTGTAGAAGCAGATGACATGGCGGCGTATATTGTTAAGCTCATCGGGCATCTTTATGATCACGTTTGGCTAATATCTACAGATGGTGACTGGGATACTTTATTAACGGATAAAGTTTCTCGTTTTTCTTTCACAACACGTCGTGAGTATCATCTTCGTGATATGTATGAGCACCATAACGTGGACGACGTAGAACAGTTTATCTCCCTGAAAGCAATTATGGGAGATCTAGGAGATAATATTCGTGGTGTTGAAGGAATAGGAGCAAAACGCGGATATAATATTATTCGTGAGTTTGGTAACGTACTGGATATTATTGATCAGCTTCCACTGCCTGGAAAGCAGAAATATATACAGAACCTGAATGCATCGGAAGAACTGCTTTTCCGAAACTTGATTCTGGTTGATTTACCTACCTACTGTGTGGATGCTATTGCTGCTGTAGGTCAAGATGTGTTAGATAAGTTCACGAAAGACATCCTTGAGATCGCGGAACAATGATAAGCTCTTAAAGGGGGTTTTAGATACCAGAGATGGATAAGAAATACTCAATAGGCTTAGATATCGGCACAAATAGCGTCGGATGGGCGGTGATCACTGATGAATATAAGGTTCCGTCTAAAAAGTTCAAGGTTCTGGGAAATACAGACCGCCACAGTATCAAAAAAAATCTTATAGGGGCTCTTTTATTTGACAGTGGAGAGACAGCGGAAGCGACTCGTCTCAAACGGACAGCTCGTAGAAGGTATACACGTCGGAAGAATCGTATTTGTTATCTACAGGAGATTTTTTCAAATGAGATGGCGAAAGTAGATGATAGTTTCTTTCATCGACTTGAAGAGTCTTTTTTGGTGGAAGAAGACAAGAAGCATGAACGTCATCCTATTTTTGGAAATATAGTAGATGAAGTTGCTTATCATGAGAAATATCCAACTATCTATCATCTGCGAAAAAAATTGGTAGATTCTACTGATAAAGCGGATTTGCGCTTAATCTATTTGGCCTTAGCGCATATGATTAAGTTTCGTGGTCATTTTTTGATTGAGGGAGATTTAAATCCTGATAATAGTGATGTGGACAAACTATTTATCCAGTTGGTACAAACCTACAATCAATTATTTGAAGAAAACCCTATTAACGCAAGTGGAGTAGATGCTAAAGCGATTCTTTCTGCACGATTGAGTAAATCAAGACGATTAGAAAATCTCATTGCTCAGCTCCCCGGTGAGAAGAAAAATGGCTTATTTGGGAATCTCATTGCTTTGTCATTGGGTTTGACCCCTAATTTTAAATCAAATTTTGATTTGGCAGAAGATGCTAAATTACAGCTTTCAAAAGATACTTACGATGATGATTTAGATAATTTATTGGCGCAAATTGGAGATCAATATGCTGATTTGTTTTTGGCAGCTAAGAATTTATCAGATGCTATTTTACTTTCAGATATCCTAAGAGTAAATACTGAAATAACTAAGGCTCCCCTATCAGCTTCAATGATTAAACGCTACGATGAACATCATCAAGACTTGACTCTTTTAAAAGCTTTAGTTCGACAACAACTTCCAGAAAAGTATAAAGAAATCTTTTTTGATCAATCAAAAAACGGATATGCAGGTTATATTGATGGGGGAGCTAGCCAAGAAGAATTTTATAAATTTATCAAACCAATTTTAGAAAAAATGGATGGTACTGAGGAATTATTGGTGAAACTAAATCGTGAAGATTTGCTGCGCAAGCAACGGACCTTTGACAACGGCTCTATTCCCCATCAAATTCACTTGGGTGAGCTGCATGCTATTTTGAGAAGACAAGAAGACTTTTATCCATTTTTAAAAGACAATCGTGAGAAGATTGAAAAAATCTTGACTTTTCGAATTCCTTATTATGTTGGTCCATTGGCGCGTGGCAATAGTCGTTTTGCATGGATGACTCGGAAGTCTGAAGAAACAATTACCCCATGGAATTTTGAAGAAGTTGTCGATAAAGGTGCTTCAGCTCAATCATTTATTGAACGCATGACAAACTTTGATAAAAATCTTCCAAATGAAAAAGTACTACCAAAACATAGTTTGCTTTATGAGTATTTTACGGTTTATAACGAATTGACAAAGGTCAAATATGTTACTGAAGGAATGCGAAAACCAGCATTTCTTTCAGGTGAACAGAAGAAAGCCATTGTTGATTTACTCTTCAAAACAAATCGAAAAGTAACCGTTAAGCAATTAAAAGAAGATTATTTCAAAAAAATAGAATGTTTTGATAGTGTTGAAATTTCAGGAGTTGAAGATAGATTTAATGCTTCATTAGGTACCTACCATGATTTGCTAAAAATTATTAAAGATAAAGATTTTTTGGATAATGAAGAAAATGAAGATATCTTAGAGGATATTGTTTTAACATTGACCTTATTTGAAGATAGGGAGATGATTGAGGAAAGACTTAAAACATATGCTCACCTCTTTGATGATAAGGTGATGAAACAGCTTAAACGTCGCCGTTATACTGGTTGGGGACGTTTGTCTCGAAAATTGATTAATGGTATTAGGGATAAGCAATCTGGCAAAACAATATTAGATTTTTTGAAATCAGATGGTTTTGCCAATCGCAATTTTATGCAGCTGATCCATGATGATAGTTTGACATTTAAAGAAGACATTCAAAAAGCACAAGTGTCTGGACAAGGCGATAGTTTACATGAACATATTGCAAATTTAGCTGGTAGCCCTGCTATTAAAAAAGGTATTTTACAGACTGTAAAAGTTGTTGATGAATTGGTCAAAGTAATGGGGCGGCATAAGCCAGAAAATATCGTTATTGAAATGGCACGTGAAAATCAGACAACTCAAAAGGGCCAGAAAAATTCGCGAGAGCGTATGAAACGAATCGAAGAAGGTATCAAAGAATTAGGAAGTCAGATTCTTAAAGAGCATCCTGTTGAAAATACTCAATTGCAAAATGAAAAGCTCTATCTCTATTATCTCCAAAATGGAAGAGACATGTATGTGGACCAAGAATTAGATATTAATCGTTTAAGTGATTATGATGTCGATCACATTGTTCCACAAAGTTTCCTTAAAGACGATTCAATAGACAATAAGGTCTTAACGCGTTCTGATAAAAATCGTGGTAAATCGGATAACGTTCCAAGTGAAGAAGTAGTCAAAAAGATGAAAAACTATTGGAGACAACTTCTAAACGCCAAGTTAATCACTCAACGTAAGTTTGATAATTTAACGAAAGCTGAACGTGGAGGTTTGAGTGAACTTGATAAAGCTGGTTTTATCAAACGCCAATTGGTTGAAACTCGCCAAATCACTAAGCATGTGGCACAAATTTTGGATAGTCGCATGAATACTAAATACGATGAAAATGATAAACTTATTCGAGAGGTTAAAGTGATTACCTTAAAATCTAAATTAGTTTCTGACTTCCGAAAAGATTTCCAATTCTATAAAGTACGTGAGATTAACAATTACCATCATGCCCATGATGCGTATCTAAATGCCGTCGTTGGAACTGCTTTGATTAAGAAATATCCAAAACTTGAATCGGAGTTTGTCTATGGTGATTATAAAGTTTATGATGTTCGTAAAATGATTGCTAAGTCTGAGCAAGAAATAGGCAAAGCAACCGCAAAATATTTCTTTTACTCTAATATCATGAACTTCTTCAAAACAGAAATTACACTTGCAAATGGAGAGATTCGCAAACGCCCTCTAATCGAAACTAATGGGGAAACTGGAGAAATTGTCTGGGATAAAGGGCGAGATTTTGCCACAGTGCGCAAAGTATTGTCCATGCCCCAAGTCAATATTGTCAAGAAAACAGAAGTACAGACAGGCGGATTCTCCAAGGAGTCAATTTTACCAAAAAGAAATTCGGACAAGCTTATTGCTCGTAAAAAAGACTGGGATCCAAAAAAATATGGTGGTTTTGATAGTCCAACGGTAGCTTATTCAGTCCTAGTGGTTGCTAAGGTGGAAAAAGGGAAATCGAAGAAGTTAAAATCCGTTAAAGAGTTACTAGGGATCACAATTATGGAAAGAAGTTCCTTTGAAAAAAATCCGATTGACTTTTTAGAAGCTAAAGGATATAAGGAAGTTAAAAAAGACTTAATCATTAAACTACCTAAATATAGTCTTTTTGAGTTAGAAAACGGTCGTAAACGGATGCTGGCTAGTGCCGGAGAATTACAAAAAGGAAATGAGCTGGCTCTGCCAAGCAAATATGTGAATTTTTTATATTTAGCTAGTCATTATGAAAAGTTGAAGGGTAGTCCAGAAGATAACGAACAAAAACAATTGTTTGTGGAGCAGCATAAGCATTATTTAGATGAGATTATTGAGCAAATCAGTGAATTTTCTAAGCGTGTTATTTTAGCAGATGCCAATTTAGATAAAGTTCTTAGTGCATATAACAAACATAGAGACAAACCAATACGTGAACAAGCAGAAAATATTATTCATTTATTTACGTTGACGAATCTTGGAGCTCCCGCTGCTTTTAAATATTTTGATACAACAATTGATCGTAAACGATATACGTCTACAAAAGAAGTTTTAGATGCCACTCTTATCCATCAATCCATCACTGGTCTTTATGAAACACGCATTGATTTGAGTCAGCTAGGAGGTGACTGATAATCAAATGTCAGACGAAAATGCCAATTATTGAAGCGGCTAACGCCGCTTTTTTTGTTTCTGGTCTCCCTTGCTTGTACTTTACAGTATAGCTTCCTCAATGATCTCCTTATCCGG >pCas9g2-D15-KinA (SEQ ID No: 242)ttaagatggcaagcttgacagccgaattcggattcccgcgTATATCTTGAATTAAAATTAAAATCTGCCAAGATCGAAAAATAAAAAGGATTTTTTGTGTCATTGGCGAATTATGATCTATTGAAGCAACCGTTAAGCTTACATAAGGAGGAACTACTATGGAACAGGATACGCAGCATGTTAAACCACTTCAAACAAAAACCGATATTCATGCAGTCTTGGCCTCTAATGGACGCATCATTTATATATCTGCCAACTCCAAACTGCATTTGGGCTATCTCCAAGGAGAGATGATCGGATCATTCCTCAAAACGTTTCTGCATGAGGAAGACCAATTTTTGGTTGAAAGCTATTTTTATAATGAACATCATCTGATGCCGTGCACCTTTCGTTTTATTAAAAAAGATCATACGATTGTGTGGGTGGAGGCTGCGGTAGAAATTGTTACGACAAGAGCTGAGCGGACAGAACGGGAAATCATTTTGAAAATGAAGGTTCTTGAAGAAGAAACAGGCCATCAATCCCTAAACTGCGAAAAACATGAAATCGAACCTGCAAGCCCGGAATCGACTACATATATAACGGATGATTATGAACGGTTGGTTGAAAATCTCCCGAGTCCGCTATGCATCAGTGTCAAAGGCAAGATCGTCTATGTAAACAGCGCGATGCTTTCAATGCTGGGAGCCAAAAGCAAGGATGCTATTATTGGTAAATCGTCCTATGAATTTATTGAAGAAGAATATCATGATATCGTGAAAAACAGGATTATACGAATGCAAAAAGGAATGGAAGTCGGAATGATTGAACAGACGTGGAAAAGGCTTGATGGCACACCTGTTCATTTAGAAGTGAAAGCATCCCCGACCGTCTACAAAAACCAGCAGGCTGAGCTGCTGCTGCTGATCGATATCTCTTCAAGGAAAAAATTCCAAACCATCCTGCAAAAAAGCCGTGAACGATATCAGCTGCTGATTCAAAATTCCATTGATACCATTGCGGTGATTCACAATGGAAAATGGGTATTTATGAATGAATCGGGAATTTCCCTGTTTGAAGCGGCTACATATGAGGATTTAATTGGCAAAAACATATACGATCAGCTGCATCCTTGCGATCACGAGGATGTAAAAGAGAGAATCCAAAACATTGCCGAGCAAAAAACAGAATCTGAAATTGTCAAGCAATCCTGGTTCACCTTTCAGAACAGGGTCATCTATACGGAGATGGTCTGCATTCCGACGACCTTTTTTGGTGAAGCGGCCGTCCAGGTCATTCTTCGGGACATCTCAGAGAGAAAACAAACAGAAGAATTGATGCTGAAATCGGAAAAATTATCAATCGCAGGGCAGCTCGCGGCGGGAATCGCCCATGAGATCCGCAACCCTCTTACAGCGATCAAAGGATTTTTACAGCTGATGAAACCGACAATGGAAGGCAACGAACATTACTTTGATATTGTGTTTTCTGAACTCAGCCGTATCGAATTAATACTCAGTGAACTGCTCATGCTGGCGAAACCTCAGCAAAATGCTGTCAAAGAATATTTGAACTTGAAAAAATTAATTGGTGAGGTTTCAGCCCTGTTAGAAACGCAGGCGAATTTAAATGGCATTTTTATCAGAACAAGTTATGAAAAAGACAGCATTTATATAAACGGGGATCAAAACCAATTAAAGCAGGTATTCATTAATTTAATCAAAAATGCAGTTGAATCAATGCCTGATGGGGGAACAGTAGACATTATCATAACCGAAGATGAGCATTCTGTTCATGTTACTGTCAAAGACGAAGGGGAAGGTATACCTGAAAAGGTACTAAACCGGATTGGAGAGCCATTTTTAACAACAAAAGAAAAAGGTACGGGGCTTGGATTAATGGTGACATTTAATATCATTGAAAACCATCAGGGAGTTATACATGTGGACAGCCATCCTGAAAAAGGCACAGCGTTTAAAATTTCATTTCcaaaaaaataagcatgcccggggatggacgagctttacaaGTAATCAAATGTCAGACGAAAATGCCAATTATTGAAGCGGCTAACGCCGCTTTTTTTGTTTCTGGTCTCCCAACTTTGCTAAAGAGCGTCTCAGCTTCTAGAGTAGAGATCTGCAGTGACTGGAGCTTCTAGAGATCAGGTCAGACGCGATTTCCTGGGTGCTCGAGCCATGGGAAAGCGGTGGTGGAAAAAACGCCGAATGAAGCGGATGAAATTGCTCATCGTCTCGTGAAAAAGCCGAAGAAGGTTAAGCCTGGGTATAAAAAGAAAATGAGCTATGAGATGGAGAAATTGAAGTCATGCGCCGGTTAGTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTTTTTTTCTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCCTCAATGATCCGACAGGAAGTGGTATTAGCGACTCCTACAAGGAATAGGTGTCTGGGTCATGCAGTGACTGGGAAAACCCTGGCGACTAGTCTTGGACTCCTGTTGATAGATCCAGTAATGACCTCAGAACTCCATCTGGATTTGTTCAGAACGCTCGGTTGCCGCCGGGCGTTTTTTATTGGTGAGAATCCAGGGGTCCCCAATAATTACGATTTAAATCCTTCAAACTTCCCAAAGGCGAGCCCTAGTGACATTAGAAAACCGACTGTAAAAAGTACAGTCGGCATTATCTCATATTATAAAAGCCAGTCATTAGGCCTATCTGACAATTCCTGAATAGAGTTCATAAACAATCCTGCATGATAACCATCACAAACAGAATGATGTACCTGTAAAGATAGCGGTAAATATATTGAATTACCTTTATTAATGAATTTTCCTGCTGTAATAATGGGTAGAAGGTAATTACTATTATTATTGATATTTAAGTTAAACCCAGTAAATGAAGTCCATGGAATAATAGAAAGAGAAAAAGCATTTTCAGGTATAGGTGTTTTGGGAAACAATTTCCCCGAACCATTATATTTCTCTACATCAGAAAGGTATAAATCATAAAACTCTTTGAAGTCATTCTTTACAGGAGTCCAAATACCAGAGAATGTTTTAGATACACCATCAAAAATTGTATAAAGTGGCTCTAACTTATCCCAATAACCTAACTCTCCGTCGCTATTGTAACCAGTTCTAAAAGCTGTATTTGAGTTTATCACCCTTGTCACTAAGAAAATAAATGCAGGGTAAAATTTATATCCTTCTTGTTTTATGTTTCGGTATAAAACACTAATATCAATTTCTGTGGTTATACTAAAAGTCGTTTGTTGGTTCAAATAATGATTAAATATCTCTTTTCTCTTCCAATTGTCTAAATCAATTTTATTAAAGTTCATTTGATATGCCTCCTAAATTTTTATCTAAAGTGAATTTAGGAGGCTTACTTGTCTGCTTTCTTCATTAGAATCAATCCTTTTTTAAAAGTCAATCCCGTTTGTTGAAGACTTTTGTCCTTTTCCGCTGCATAAACAATATGGCCCGTTTGTTGAACTACTCTTTAATAAAATAATTTTTCCGTTCCCAATTCCACATTGCAATAATAGAAAATCCATCTTCATCGGCTTTTTCGTCATCATCTGTATGAATCAAATCGCCTTCTTCTGTGTCATCAAGGTTTAATTTTTTATGTATTTCTTTTAACAAACCACCATAGGAGATTAACCTTTTACGGTGTAAACCTTCCTCCAAATCAGACAAACGTTTCAAATTCTTTTCTTCATCATCGGTCATAAAATCCGTATCCTTTACAGGATATTTTGCAGTTTCGTCAATTGCCGATTGTATATCCGATTTATATTTATTTTTCGGTCGAATCATTTGAACTTTTACATTTGGATCATAGTCTAATTTCATTGCCTTTTTCCAAAATTGAATCCATTGTTTTTGATTCACGTAGTTTTCTGTATTCTTAAAATAAGTTGGTTCCACACATACCAATACATGCATGTGCTGATTATAAGAATTATCTTTATTATTTATTGTCACTTCCGTTGCACGCATAAAACCAACAAGATTTTTATTAATTTTTTTATATTGCATCATTCGGCGAAATCCTTGAGCCATATCTGACAAACTCTTATTTAATTCTTCGCCATCATAAACATTTTTAACTGTTAATGTGAGAAACAACCAACGAACTGTTGGCTTTTGTTTAATAACTTCAGCAACAACCTTTTGTGACTGAATGCCATGTTTCATTGCTCTCCTCCAGTTGCACATTGGACAAAGCCTGGATTTACAAAACCACACTCGATACAACTTTCTTTCGCCTGTTTCACGATTTTGTTTATACTCTAATATTTCAGCACAATCTTTTACTCTTTCAGCCTTTTTAAATTCAAGAATATGCAGAAGTTCAAAGTAATCAACATTAGCGATTTTCTTTTCTCTCCATGGTCTCACTTTTCCACTTTTTGTCTTGTCCACTAAAACCCTTGATTTTTCATCTGAATAAATGCTACTATTAGGACACATAATATTAAAAGAAACCCCCATCTATTTAGTTATTTGTTTGGTCACTTATAACTTTAACAGATGGGGTTTTTCTGTGCAACCAATTTTAAGGGTTTTCCAATACTTTAAAACACATACATACCAACACTTCAACGCACCTTTCAGCAACTAAAATAAAAATGACGTTATTTCTATATGTATCAAGATAAGAAAGAACAAGTTCAAAACCATCAAAAAAAGACACCTTTTCAGGTGCTTTTTTTATTTTATAAACTCATTCCCTGATCTCGACTTCGTTCTTTTTTTACCTCTCGGTTATGAGTTAGTTCAAATTCGTTCTTTTTAGGTTCTAAATCGTGTTTTTCTTGGAATTGTGCTGTTTTATCCTTTACCTTGTCTACAAACCCCTTAAAAACGTTTTTAAAGGCTTTTAAGCGTCTGTACGTTCCTTAAGGAATTATTCCTTAGTGCTTTCTAGGTTAATGTCATGATAATAATGGTTTCTTAGACGTCAGGTGGCACTTTTCGGGGAAATGTCCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAAGAGTATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTGTTGACGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGCAGCAATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAATCTGGAGCCGGTGAGCGTGGGTCTCGCGGTATCATTGCAGCACTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGTAACTGTCAGACCAAGTTTACTCATATATACTTTAGATTGATTTAAAACTTCATTTTTAATTTAAAAGGATCTAGGTGAAGATCCTTTTTGATAATCTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTGAGCGTCAGACCCCTTAATAAGATGATCTTCTTGAGATCGTTTTGGTCTGCGCGTAATCTCTTGCTCTGAAAACGAAAAAACCGCCTTGCAGGGAGGTTTTTCGAAGGTTCTCTGAGCTACCAACTCTTTGAACCGAGGTAACTGGCTTGCAGGAGCGCAGTCACCAAAACTTGTCCTTTCAGTTTAGCCTTAACCGGCGCATGACTTCAAGACTAACTCCTCTAAATCAATTACCAGTGGCTGCTGCCAGTGGTGCTTTTGCATGTCTTTCCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGGACTGAACGGGGGGTTCGTGCATACAGTCCAGCTTGGAGCGAACTGCCTACCCGGAACTGAGTGTCAGGCGTGGAATGAGACAAACGCGGCCATAACAGCGGAATGACACCGGTAAACCGAAAGGCAGGAACAGGAGAGCGCACGAGGGAGCCGCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGTTTCGCCACCACTGATTTGAGCGTCAGATTTCGTGATGCTTGTCAGGGGGCGGAGCCTATGGAAAAACGCTTTGCCCGAGCCTATGGAAAAACGCTTTGCCCCACACAGGCTCTTGAACAAGGGATAACAATTTGTCATAGCTGTATTCGTTACAAGGAGGATTTTCGAAAAAACACCCTAACGGGTGTTTTTTTATAGCTGGTCTCCCCAAGTGCTGTAAAAAACGCCGAATGAAGCGGATGAAATTGCTCATCGTCTCGTGAAAAAGCCGAAGAAGGTTAAGCCTGGGTATAAAAAGAAAATGAGCTATGAGATGGAGAAAGCCATAACCATGAGTGATAACACTGGTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGCTAGTCCGTTATCAACTTGAAAAAGTGGCACCGAGTCGGTGCTTTTTTTCTCGGTACCAAATTCCAGAAAAGAGGCCTCCCGAAAGGGGGGCCTTTTTTCGTTTTGGTCCCTCAATGATCTCCTTATCCGGTTAAGATGGCTTTTAAATCAATTTTCAGCTCCTGTATACAATTACCAAAGTTTTTCTGAATGAAGCCATGTGTTTTGACACATTCTATACTCACAAGGAGGTGAGACACATGAGTAAATCCTGGGGCAAATTCATCGAGGAGGAAGAGGCGGAAATGGCTTCCCGTCGTAATCTAATGATTGTCGATGGAACTAACTTAGGCTTTCGCTTCAAACATAACAATAGTAAAAAACCATTTGCCTCAAGTTATGTTTCAACTATTCAATCTCTGGCAAAATCCTACTCTGCCAGAACTACGATTGTTCTAGGTGATAAGGGCAAAAGCGTGTTCAGACTAGAACATCTACCAGAGTATAAAGGTAATCGTGATGAAAAGTACGCACAACGTACGGAAGAGGAGAAAGCGCTAGATGAGCAGTTCTTCGAATACCTCAAAGATGCTTTCGAGTTGTGTAAAACTACATTCCCAACTTTTACCATTCGTGGTGTAGAAGCAGATGACATGGCGGCGTATATTGTTAAGCTCATCGGGCATCTTTATGATCACGTTTGGCTAATATCTACAGATGGTGACTGGGATACTTTATTAACGGATAAAGTTTCTCGTTTTTCTTTCACAACACGTCGTGAGTATCATCTTCGTGATATGTATGAGCACCATAACGTGGACGACGTAGAACAGTTTATCTCCCTGAAAGCAATTATGGGAGATCTAGGAGATAATATTCGTGGTGTTGAAGGAATAGGAGCAAAACGCGGATATAATATTATTCGTGAGTTTGGTAACGTACTGGATATTATTGATCAGCTTCCACTGCCTGGAAAGCAGAAATATATACAGAACCTGAATGCATCGGAAGAACTGCTTTTCCGAAACTTGATTCTGGTTGATTTACCTACCTACTGTGTGGATGCTATTGCTGCTGTAGGTCAAGATGTGTTAGATAAGTTCACGAAAGACATCCTTGAGATCGCGGAACAATGATAAGCTCTTAAAGGGGGTTTTAGATACCAGAGATGGATAAGAAATACTCAATAGGCTTAGATATCGGCACAAATAGCGTCGGATGGGCGGTGATCACTGATGAATATAAGGTTCCGTCTAAAAAGTTCAAGGTTCTGGGAAATACAGACCGCCACAGTATCAAAAAAAATCTTATAGGGGCTCTTTTATTTGACAGTGGAGAGACAGCGGAAGCGACTCGTCTCAAACGGACAGCTCGTAGAAGGTATACACGTCGGAAGAATCGTATTTGTTATCTACAGGAGATTTTTTCAAATGAGATGGCGAAAGTAGATGATAGTTTCTTTCATCGACTTGAAGAGTCTTTTTTGGTGGAAGAAGACAAGAAGCATGAACGTCATCCTATTTTTGGAAATATAGTAGATGAAGTTGCTTATCATGAGAAATATCCAACTATCTATCATCTGCGAAAAAAATTGGTAGATTCTACTGATAAAGCGGATTTGCGCTTAATCTATTTGGCCTTAGCGCATATGATTAAGTTTCGTGGTCATTTTTTGATTGAGGGAGATTTAAATCCTGATAATAGTGATGTGGACAAACTATTTATCCAGTTGGTACAAACCTACAATCAATTATTTGAAGAAAACCCTATTAACGCAAGTGGAGTAGATGCTAAAGCGATTCTTTCTGCACGATTGAGTAAATCAAGACGATTAGAAAATCTCATTGCTCAGCTCCCCGGTGAGAAGAAAAATGGCTTATTTGGGAATCTCATTGCTTTGTCATTGGGTTTGACCCCTAATTTTAAATCAAATTTTGATTTGGCAGAAGATGCTAAATTACAGCTTTCAAAAGATACTTACGATGATGATTTAGATAATTTATTGGCGCAAATTGGAGATCAATATGCTGATTTGTTTTTGGCAGCTAAGAATTTATCAGATGCTATTTTACTTTCAGATATCCTAAGAGTAAATACTGAAATAACTAAGGCTCCCCTATCAGCTTCAATGATTAAACGCTACGATGAACATCATCAAGACTTGACTCTTTTAAAAGCTTTAGTTCGACAACAACTTCCAGAAAAGTATAAAGAAATCTTTTTTGATCAATCAAAAAACGGATATGCAGGTTATATTGATGGGGGAGCTAGCCAAGAAGAATTTTATAAATTTATCAAACCAATTTTAGAAAAAATGGATGGTACTGAGGAATTATTGGTGAAACTAAATCGTGAAGATTTGCTGCGCAAGCAACGGACCTTTGACAACGGCTCTATTCCCCATCAAATTCACTTGGGTGAGCTGCATGCTATTTTGAGAAGACAAGAAGACTTTTATCCATTTTTAAAAGACAATCGTGAGAAGATTGAAAAAATCTTGACTTTTCGAATTCCTTATTATGTTGGTCCATTGGCGCGTGGCAATAGTCGTTTTGCATGGATGACTCGGAAGTCTGAAGAAACAATTACCCCATGGAATTTTGAAGAAGTTGTCGATAAAGGTGCTTCAGCTCAATCATTTATTGAACGCATGACAAACTTTGATAAAAATCTTCCAAATGAAAAAGTACTACCAAAACATAGTTTGCTTTATGAGTATTTTACGGTTTATAACGAATTGACAAAGGTCAAATATGTTACTGAAGGAATGCGAAAACCAGCATTTCTTTCAGGTGAACAGAAGAAAGCCATTGTTGATTTACTCTTCAAAACAAATCGAAAAGTAACCGTTAAGCAATTAAAAGAAGATTATTTCAAAAAAATAGAATGTTTTGATAGTGTTGAAATTTCAGGAGTTGAAGATAGATTTAATGCTTCATTAGGTACCTACCATGATTTGCTAAAAATTATTAAAGATAAAGATTTTTTGGATAATGAAGAAAATGAAGATATCTTAGAGGATATTGTTTTAACATTGACCTTATTTGAAGATAGGGAGATGATTGAGGAAAGACTTAAAACATATGCTCACCTCTTTGATGATAAGGTGATGAAACAGCTTAAACGTCGCCGTTATACTGGTTGGGGACGTTTGTCTCGAAAATTGATTAATGGTATTAGGGATAAGCAATCTGGCAAAACAATATTAGATTTTTTGAAATCAGATGGTTTTGCCAATCGCAATTTTATGCAGCTGATCCATGATGATAGTTTGACATTTAAAGAAGACATTCAAAAAGCACAAGTGTCTGGACAAGGCGATAGTTTACATGAACATATTGCAAATTTAGCTGGTAGCCCTGCTATTAAAAAAGGTATTTTACAGACTGTAAAAGTTGTTGATGAATTGGTCAAAGTAATGGGGCGGCATAAGCCAGAAAATATCGTTATTGAAATGGCACGTGAAAATCAGACAACTCAAAAGGGCCAGAAAAATTCGCGAGAGCGTATGAAACGAATCGAAGAAGGTATCAAAGAATTAGGAAGTCAGATTCTTAAAGAGCATCCTGTTGAAAATACTCAATTGCAAAATGAAAAGCTCTATCTCTATTATCTCCAAAATGGAAGAGACATGTATGTGGACCAAGAATTAGATATTAATCGTTTAAGTGATTATGATGTCGATCACATTGTTCCACAAAGTTTCCTTAAAGACGATTCAATAGACAATAAGGTCTTAACGCGTTCTGATAAAAATCGTGGTAAATCGGATAACGTTCCAAGTGAAGAAGTAGTCAAAAAGATGAAAAACTATTGGAGACAACTTCTAAACGCCAAGTTAATCACTCAACGTAAGTTTGATAATTTAACGAAAGCTGAACGTGGAGGTTTGAGTGAACTTGATAAAGCTGGTTTTATCAAACGCCAATTGGTTGAAACTCGCCAAATCACTAAGCATGTGGCACAAATTTTGGATAGTCGCATGAATACTAAATACGATGAAAATGATAAACTTATTCGAGAGGTTAAAGTGATTACCTTAAAATCTAAATTAGTTTCTGACTTCCGAAAAGATTTCCAATTCTATAAAGTACGTGAGATTAACAATTACCATCATGCCCATGATGCGTATCTAAATGCCGTCGTTGGAACTGCTTTGATTAAGAAATATCCAAAACTTGAATCGGAGTTTGTCTATGGTGATTATAAAGTTTATGATGTTCGTAAAATGATTGCTAAGTCTGAGCAAGAAATAGGCAAAGCAACCGCAAAATATTTCTTTTACTCTAATATCATGAACTTCTTCAAAACAGAAATTACACTTGCAAATGGAGAGATTCGCAAACGCCCTCTAATCGAAACTAATGGGGAAACTGGAGAAATTGTCTGGGATAAAGGGCGAGATTTTGCCACAGTGCGCAAAGTATTGTCCATGCCCCAAGTCAATATTGTCAAGAAAACAGAAGTACAGACAGGCGGATTCTCCAAGGAGTCAATTTTACCAAAAAGAAATTCGGACAAGCTTATTGCTCGTAAAAAAGACTGGGATCCAAAAAAATATGGTGGTTTTGATAGTCCAACGGTAGCTTATTCAGTCCTAGTGGTTGCTAAGGTGGAAAAAGGGAAATCGAAGAAGTTAAAATCCGTTAAAGAGTTACTAGGGATCACAATTATGGAAAGAAGTTCCTTTGAAAAAAATCCGATTGACTTTTTAGAAGCTAAAGGATATAAGGAAGTTAAAAAAGACTTAATCATTAAACTACCTAAATATAGTCTTTTTGAGTTAGAAAACGGTCGTAAACGGATGCTGGCTAGTGCCGGAGAATTACAAAAAGGAAATGAGCTGGCTCTGCCAAGCAAATATGTGAATTTTTTATATTTAGCTAGTCATTATGAAAAGTTGAAGGGTAGTCCAGAAGATAACGAACAAAAACAATTGTTTGTGGAGCAGCATAAGCATTATTTAGATGAGATTATTGAGCAAATCAGTGAATTTTCTAAGCGTGTTATTTTAGCAGATGCCAATTTAGATAAAGTTCTTAGTGCATATAACAAACATAGAGACAAACCAATACGTGAACAAGCAGAAAATATTATTCATTTATTTACGTTGACGAATCTTGGAGCTCCCGCTGCTTTTAAATATTTTGATACAACAATTGATCGTAAACGATATACGTCTACAAAAGAAGTTTTAGATGCCACTCTTATCCATCAATCCATCACTGGTCTTTATGAAACACGCATTGATTTGAGTCAGCTAGGAGGTGACTGATAATCAAATGTCAGACGAAAATGCCAATTATTGAAGCGGCTAACGCCGCTTTTTTTGTTTCTGGTCTCCCTTGCTTGTACTTTACAGTATAGCTTCCTCAATGATCTCCTTATCCGG

The scope of the present invention is not limited by what has beenspecifically shown and described hereinabove. Those skilled in the artwill recognize that there are suitable alternatives to the depictedexamples of materials, configurations, constructions and dimensions.Numerous references, including patents and various publications, arecited and discussed in the description of this invention. The citationand discussion of such references is provided merely to clarify thedescription of the present invention and is not an admission that anyreference is prior art to the invention described herein. All referencescited and discussed in this specification are incorporated herein byreference in their entirety. Variations, modifications and otherimplementations of what is described herein will occur to those ofordinary skill in the art without departing from the spirit and scope ofthe invention. While certain embodiments of the present invention havebeen shown and described, it will be obvious to those skilled in the artthat changes and modifications may be made without departing from thespirit and scope of the invention. The matter set forth in the foregoingdescription is offered by way of illustration only and not as alimitation.

1. A method of producing a modified microbial spore, the methodcomprising: introducing at least one vector into a spore-formingmicroorganism, wherein the at least one vector encodes (i) asequence-specific endonuclease system which targets the at least onevector, and (ii) an exogenous gene product, wherein the endonucleasesystem is operably linked to a spore-specific promoter, and culturingthe spore-forming microorganism to generate a modified microbial spore.2. The method of claim 1, wherein the at least one vector furtherencodes an exonuclease.
 3. The method of claim 1, wherein the at leastone vector comprises a vector encoding the sequence-specificendonuclease system and the exogenous gene product.
 4. The method ofclaim 1, wherein the spore-forming microorganism is a spore-formingbacterium or a spore-forming fungus.
 5. The method of claim 4, whereinthe spore-forming bacterium is Bacillus subtilis, Bacillus firmus,Bacillus megaterium, Bacillus amyloliquefaciens, Bacillus licheniformis,or Bacillus pumilus.
 6. The method of claim 1, wherein thesequence-specific endonuclease system comprises an RNA-guidedendonuclease.
 7. The method of claim 6, wherein the RNA-guidedendonuclease comprises a CRISPR/Cas system.
 8. The method of claim 6,wherein the RNA-guided DNA endonuclease is a Cas enzyme or a variantthereof.
 9. The method of claim 8, wherein the Cas enzyme is Cas9. 10.The method of claim 1, wherein the at least one vector encodes a Casenzyme and a guide RNA (gRNA).
 11. The method of claim 1, wherein the atleast one vector encodes a Cas enzyme and two gRNAs.
 12. The method ofclaim 2, wherein the exonuclease is D15.
 13. The method of claim 1,wherein the spore-specific promoter is PsspA.
 14. The method of claim 1,wherein the at least one vector is a plasmid.
 15. The method of claim 1,wherein the exogenous gene product is a protein.
 16. The method of claim1, wherein the exogenous gene product is an enzyme.
 17. A phenotypicallymodified microbial spore, comprising an exogenous gene product, whereinthe microbial spore is substantially free of exogenous genes.
 18. Thespore of claim 17, wherein the microbial spore is a bacterial spore or afungal spore.
 19. The spore of claim 17, wherein the exogenous geneproduct is a protein.
 20. A composition comprising the microbial sporeof claim 17.